Pathways to neurodegeneration: Mechanistic insights from GWAS in Alzheimer’s disease, Parkinson’s disease, and related disorders

American Journal of Neurodegenerative Diseases

Volumn 2, Issue 3, 2013, Pages 145-175

  Ramanan, Vijay K ^a   Saykin, Andrew J ^a  

^a INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Alzheimer s disease (AD); Biomarker; Complex disease; Genome wide association study (GWAS); Network; Neurodegeneration; Omics; Parkinson s disease (PD); Pathway; Single nucleotide polymorphism (SNP)

Indexed keywords

APOLIPOPROTEIN E; PRION PROTEIN; PROTEASOME; UBIQUITIN;

AGING; ALZHEIMER DISEASE; APOPTOSIS; AUTOPHAGY; CELL ADHESION; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DNA DAMAGE; DNA REPAIR; ENDOCYTOSIS; EPIGENETICS; GENETIC ASSOCIATION; HUMAN; META ANALYSIS (TOPIC); NERVE CELL DIFFERENTIATION; NEUROTRANSMISSION; NONHUMAN; OXIDATIVE STRESS; PARKINSONISM; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; TELOMERE; UPREGULATION;

EID: 84980053612     PISSN: None     EISSN: 2165591X     Source Type: Journal    
DOI: None     Document Type: Review

References (328)

1. Hardy JA and Higgins GA. Alzheimer's disease: the amyloid cascade hypothesis. Science 1992; 256: 184-185.
2. Karran E, Mercken M and De Strooper B. The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov 2011; 10: 698-712.
3. Taylor JP, Hardy J and Fischbeck KH. Toxic proteins in neurodegenerative disease. Science 2002; 296: 1991-1995.
4. Krainc D. Clearance of mutant proteins as a therapeutic target in neurodegenerative diseases. Arch Neurol 2010; 67: 388-392.
5. Rademakers R, Neumann M and Mackenzie IR. Advances in understanding the molecular basis of frontotemporal dementia. Nat Rev Neurol 2012; 8: 423-434.
6. Sleegers K, Lambert JC, Bertram L, Cruts M, Amouyel P and Van Broeckhoven C. The pursuit of susceptibility genes for Alzheimer's disease: progress and prospects. Trends Genet 2010; 26: 84-93.
7. Hardy J. Genetic analysis of pathways to Parkinson disease. Neuron 2010; 68: 201-206.
8. Gandhi S and Wood NW. Genome-wide association studies: the key to unlocking neurodegeneration? Nat Neurosci 2010; 13: 789-794.
9. Bertram L and Tanzi RE. The genetic epidemiology of neurodegenerative disease. J Clin Invest 2005; 115: 1449-1457.
10. McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J, Ioannidis JP and Hirschhorn JN. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet 2008; 9: 356-369.
11. Chee Seng K, En Yun L, Yudi P and Kee Seng C. The pursuit of genome-wide association studies: where are we now? J Hum Genet 2010; 55: 195-206.
12. Noorbakhsh F, Overall CM and Power C. Deciphering complex mechanisms in neurodegenerative diseases: the advent of systems biology. Trends Neurosci 2009; 32: 88-100.
13. Hindorff LA, Junkins HA, Hall PN, Mehta JP and Manolio TA. A Catalog of Published Genome-Wide Association Studies. National Human Genome Research Institute, http://www.genome.gov/gwastudies 2011.
14. Gatz M, Reynolds CA, Fratiglioni L, Johansson B, Mortimer JA, Berg S, Fiske A and Pedersen NL. Role of genes and environments for explaining Alzheimer disease. Arch Gen Psychiatry 2006; 63: 168-174.
15. Kamboh MI, Demirci FY, Wang X, Minster RL, Carrasquillo MM, Pankratz VS, Younkin SG, Saykin AJ, Jun G, Baldwin C, Logue MW, Buros J, Farrer L, Pericak-Vance MA, Haines JL, Sweet RA, Ganguli M, Feingold E, DeKosky ST, Lopez OL and Barmada MM. Genome-wide association study of Alzheimer's disease. Transl Psychiatry 2012; 2: e117.
16. Cross-Disorder Group of the Psychiatric Genomics Consortium; Smoller JW, Craddock N, Kendler K, Lee PH, Neale BM, Nurnberger JI, Ripke S, Santangelo S, Sullivan PF. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 2013 Apr 20; 381: 1371-9.
17. Simon-Sanchez J and Singleton A. Genome-wide association studies in neurological disorders. Lancet Neurol 2008; 7: 1067-1072.
18. Cantor RM, Lange K and Sinsheimer JS. Prioritizing GWAS results: A review of statistical methods and recommendations for their application. Am J Hum Genet 2010; 86: 6-22.
19. Ramanan VK, Shen L, Moore JH and Saykin AJ. Pathway analysis of genomic data: concepts, methods, and prospects for future development. Trends Genet 2012; 28: 323-332.
20. Wang K, Li M and Hakonarson H. Analysing biological pathways in genome-wide association studies. Nat Rev Genet 2010; 11: 843-854.
21. Lambert JC, Grenier-Boley B, Chouraki V, Heath S, Zelenika D, Fievet N, Hannequin D, Pasquier F, Hanon O, Brice A, Epelbaum J, Berr C, Dartigues JF, Tzourio C, Campion D, Lathrop M and Amouyel P. Implication of the immune system in Alzheimer's disease: evidence from genome-wide pathway analysis. J Alzheimers Dis 2010; 20: 1107-1118.
22. Hong MG, Alexeyenko A, Lambert JC, Amouyel P and Prince JA. Genome-wide pathway analysis implicates intracellular transmembrane protein transport in Alzheimer disease. J Hum Genet 2010; 55: 707-709.
23. Ramanan VK, Kim S, Holohan K, Shen L, Nho K, Risacher SL, Foroud TM, Mukherjee S, Crane PK, Aisen PS, Petersen RC, Weiner MW, Saykin AJ; Alzheimer's Disease Neuroimaging Initiative (ADNI). Genome-wide pathway analysis of memory impairment in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort implicates gene candidates, canonical pathways, and networks. Brain Imaging Behav 2012; 6: 634-648.
24. O'Dushlaine C, Kenny E, Heron E, Donohoe G, Gill M, Morris D and Corvin A. Molecular pathways involved in neuronal cell adhesion and membrane scaffolding contribute to schizophrenia and bipolar disorder susceptibility. Mol Psychiatry 2011; 16: 286-292.
25. O'Dushlaine C, Kenny E, Heron EA, Segurado R, Gill M, Morris DW and Corvin A. The SNP ratio test: pathway analysis of genome-wide association datasets. Bioinformatics 2009; 25: 2762-2763.
26. Baranzini SE, Galwey NW, Wang J, Khankhanian P, Lindberg R, Pelletier D, Wu W, Uitdehaag BM, Kappos L, Polman CH, Matthews PM, Hauser SL, Gibson RA, Oksenberg JR and Barnes MR. Pathway and network-based analysis of genome-wide association studies in multiple sclerosis. Hum Mol Genet 2009; 18: 2078-2090.
27. Sawcer S, Hellenthal G, Pirinen M, Spencer C, Patsopoulos N, Moutsianas L, Dilthey A, Su Z, Freeman C, Hunt S, Edkins S, Gray E, Booth D, Potter SC, Goris A, Band G, Oturai AB, Strange A, Saarela J, Bellenguez C, Fontaine B, Gillman M, Hemmer B, Gwilliam R, Zipp F, Jayakumar A, Martin R, Leslie S, Hawkins S, Giannoulatou E, D'alfonso S, Blackburn H, Boneschi FM, Liddle J, Harbo HF, Perez ML, Spurkland A, Waller MJ, Mycko MP, Ricketts M, Comabella M, Hammond N, Kockum I, McCann OT, Ban M, Whittaker P, Kemppinen A, Weston P, Hawkins C, Widaa S, Zajicek J, Dronov S, Robertson N, Bumpstead SJ, Barcellos LF, Ravindrarajah R, Abraham R, Alfredsson L, Ardlie K, Aubin C, Baker A, Baker K, Baranzini SE, Bergamaschi L, Bergamaschi R, Bernstein A, Berthele A, Boggild M, Bradfield JP, Brassat D, Broadley SA, Buck D, Butzkueven H, Capra R, Carroll WM, Cavalla P, Celius EG, Cepok S, Chiavacci R, Clerget-Darpoux F, Clysters K, Comi G, Cossburn M, Cournu-Rebeix I, Cox MB, Cozen W, Cree BA, Cross AH, Cusi D, Daly MJ, Davis E, de Bakker PI, Debouverie M, D'hooghe MB, Dixon K, Dobosi R, Dubois B, Ellinghaus D, Elovaara I, Esposito F, Fontenille C, Foote S, Franke A, Galimberti D, Ghezzi A, Glessner J, Gomez R, Gout O, Graham C, Grant SF, Guerini FR, Hakonarson H, Hall P, Hamsten A, Hartung HP, Heard RN, Heath S, Hobart J, Hoshi M, Infante-Duarte C, Ingram G, Ingram W, Islam T, Jagodic M, Kabesch M, Kermode AG, Kilpatrick TJ, Kim C, Klopp N, Koivisto K, Larsson M, Lathrop M, Lechner-Scott JS, Leone MA, Leppä V, Liljedahl U, Bomfim IL, Lincoln RR, Link J, Liu J, Lorentzen AR, Lupoli S, Macciardi F, Mack T, Marriott M, Martinelli V, Mason D, McCauley JL, Mentch F, Mero IL, Mihalova T, Montalban X, Mottershead J, Myhr KM, Naldi P, Ollier W, Page A, Palotie A, Pelletier J, Piccio L, Pickersgill T, Piehl F, Pobywajlo S, Quach HL, Ramsay PP, Reunanen M, Reynolds R, Rioux JD, Rodegher M, Roesner S, Rubio JP, Rückert IM, Salvetti M, Salvi E, Santaniello A, Schaefer CA, Schreiber S, Schulze C, Scott RJ, Sellebjerg F, Selmaj KW, Sexton D, Shen L, Simms-Acuna B, Skidmore S, Sleiman PM, Smestad C, Sørensen PS, Søndergaard HB, Stankovich J, Strange RC, Sulonen AM, Sundqvist E, Syvänen AC, Taddeo F, Taylor B, Blackwell JM, Tienari P, Bramon E, Tourbah A, Brown MA, Tronczynska E, Casas JP, Tubridy N, Corvin A, Vickery J, Jankowski J, Villoslada P, Markus HS, Wang K, Mathew CG, Wason J, Palmer CN, Wichmann HE, Plomin R, Willoughby E, Rautanen A, Winkelmann J, Wittig M, Trembath RC, Yaouanq J, Viswanathan AC, Zhang H, Wood NW, Zuvich R, Deloukas P, Langford C, Duncanson A, Oksenberg JR, Pericak-Vance MA, Haines JL, Olsson T, Hillert J, Ivinson AJ, De Jager PL, Peltonen L, Stewart GJ, Hafler DA, Hauser SL, McVean G, Donnelly P, Compston A. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2011; 476: 214-219.
28. Psychiatric GWAS Consortium Bipolar Disorder Working Group. Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat Genet 2011; 43: 977-983.
29. Hirschhorn JN. Genomewide Association Studies - Illuminating Biologic Pathways. N Engl J Med 2009; 360: 1699-1701.
30. Penrod NM, Cowper-Sallari R and Moore JH. Systems genetics for drug target discovery. Trends Pharmacol Sci 2011; 32: 623-630.
31. Bras J, Guerreiro R and Hardy J. Use of next-generation sequencing and other whole-genome strategies to dissect neurological disease. Nat Rev Neurosci 2012; 13: 453-464.
32. Braskie MN, Ringman JM and Thompson PM. Neuroimaging measures as endophenotypes in Alzheimer's disease. Int J Alzheimers Dis 2011; 2011: 490140.
33. Kendler KS and Neale MC. Endophenotype: a conceptual analysis. Mol Psychiatry 2010; 15: 789-797.
34. Cruchaga C, Kauwe JS, Nowotny P, Bales K, Pickering EH, Mayo K, Bertelsen S, Hinrichs A; Alzheimer's Disease Neuroimaging Initiative; Fagan AM, Holtzman DM, Morris JC, Goate AM. Cerebrospinal fluid APOE levels: an endophenotype for genetic studies for Alzheimer's disease. Hum Mol Genet 2012 Oct 15; 21: 4558-71.
35. Jack CR Jr, Vemuri P, Wiste HJ, Weigand SD, Lesnick TG, Lowe V, Kantarci K, Bernstein MA, Senjem ML, Gunter JL, Boeve BF, Trojanowski JQ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Knopman DS; Alzheimer's Disease Neuroimaging Initiative. Shapes of the Trajectories of 5 Major Biomarkers of Alzheimer Disease. Arch Neurol 2012; 69: 856-867.
36. McKinney BA and Pajewski NM. Six Degrees of Epistasis: Statistical Network Models for GWAS. Front Genet 2011; 2: 109.
37. Vidal M, Cusick ME and Barabasi AL. Interactome networks and human disease. Cell 2011; 144: 986-998.
38. Schadt EE. Molecular networks as sensors and drivers of common human diseases. Nature 2009; 461: 218-223.
39. Nussbaum RL and Ellis CE. Alzheimer's Disease and Parkinson's Disease. N Engl J Med 2003; 348: 1356-1364.
40. Bredesen DE, Rao RV and Mehlen P. Cell death in the nervous system. Nature 2006; 443: 796-802.
41. Mattson MP. Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol 2000; 1: 120-129.
42. Loo DT, Copani A, Pike CJ, Whittemore ER, Walencewicz AJ and Cotman CW. Apoptosis Is Induced by Beta-Amyloid in Cultured Central-Nervous-System Neurons. Proc Natl Acad Sci U S A 1993; 90: 7951-7955.
43. Wolozin B, Iwasaki K, Vito P, Ganjei JK, Lacana E, Sunderland T, Zhao B, Kusiak JW, Wasco W and D'Adamio L. Participation of presenilin 2 in apoptosis: enhanced basal activity conferred by an Alzheimer mutation. Science 1996; 274: 1710-1713.
44. Weidemann A, Paliga K, Durrwang U, Reinhard FBM, Schuckert O, Evin G and Masters CL. Proteolytic processing of the Alzheimer's disease amyloid precursor protein within its cytoplasmic domain by caspase-like proteases. J Biol Chem 1999; 274: 5823-5829.
45. Guo Q, Sebastian L, Sopher BL, Miller MW, Glazner GW, Ware CB, Martin GM and Mattson MP. Neurotrophic factors [activity-dependent neurotrophic factor (ADNF) and basic fibroblast growth factor (bFGF)] interrupt excitotoxic neurodegenerative cascades promoted by a PS1 mutation. Proc Natl Acad Sci U S A 1999; 96: 4125-4130.
46. Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL and Pericak-Vance MA. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 1993; 261: 921-923.
47. Koffie RM, Hashimoto T, Tai HC, Kay KR, Serrano-Pozo A, Joyner D, Hou S, Kopeikina KJ, Frosch MP, Lee VM, Holtzman DM, Hyman BT and Spires-Jones TL. Apolipoprotein E4 effects in Alzheimer's disease are mediated by synaptotoxic oligomeric amyloid-beta. Brain 2012; 135: 2155-2168.
48. Soler-Lopez M, Zanzoni A, Lluis R, Stelzl U and Aloy P. Interactome mapping suggests new mechanistic details underlying Alzheimer's disease. Genome Res 2011; 21: 364-376.
49. Lambert JC, Heath S, Even G, Campion D, Sleegers K, Hiltunen M, Combarros O, Zelenika D, Bullido MJ, Tavernier B, Letenneur L, Bettens K, Berr C, Pasquier F, Fievet N, Barberger-Gateau P, Engelborghs S, De Deyn P, Mateo I, Franck A, Helisalmi S, Porcellini E, Hanon O, de Pancorbo MM, Lendon C, Dufouil C, Jaillard C, Leveillard T, Alvarez V, Bosco P, Mancuso M, Panza F, Nacmias B, Bossu P, Piccardi P, Annoni G, Seripa D, Galimberti D, Hannequin D, Licastro F, Soininen H, Ritchie K, Blanche H, Dartigues JF, Tzourio C, Gut I, Van Broeckhoven C, Alperovitch A, Lathrop M and Amouyel P. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Nat Genet 2009; 41: 1094-1099.
50. Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A, Hamshere ML, Pahwa JS, Moskvina V, Dowzell K, Williams A, Jones N, Thomas C, Stretton A, Morgan AR, Lovestone S, Powell J, Proitsi P, Lupton MK, Brayne C, Rubinsztein DC, Gill M, Lawlor B, Lynch A, Morgan K, Brown KS, Passmore PA, Craig D, McGuinness B, Todd S, Holmes C, Mann D, Smith AD, Love S, Kehoe PG, Hardy J, Mead S, Fox N, Rossor M, Collinge J, Maier W, Jessen F, Schurmann B, van den Bussche H, Heuser I, Kornhuber J, Wiltfang J, Dichgans M, Frolich L, Hampel H, Hull M, Rujescu D, Goate AM, Kauwe JSK, Cruchaga C, Nowotny P, Morris JC, Mayo K, Sleegers K, Bettens K, Engelborghs S, De Deyn PP, Van Broeckhoven C, Livingston G, Bass NJ, Gurling H, McQuillin A, Gwilliam R, Deloukas P, Al-Chalabi A, Shaw CE, Tsolaki M, Singleton AB, Guerreiro R, Muhleisen TW, Nothen MM, Moebus S, Jockel KH, Klopp N, Wichmann HE, Carrasquillo MM, Pankratz VS, Younkin SG, Holmans PA, O'Donovan M, Owen MJ and Williams J. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nat Genet 2009; 41: 1088-1093.
51. Hollingworth P, Harold D, Sims R, Gerrish A, Lambert JC, Carrasquillo MM, Abraham R, Hamshere ML, Pahwa JS, Moskvina V, Dowzell K, Jones N, Stretton A, Thomas C, Richards A, Ivanov D, Widdowson C, Chapman J, Lovestone S, Powell J, Proitsi P, Lupton MK, Brayne C, Rubinsztein DC, Gill M, Lawlor B, Lynch A, Brown KS, Passmore PA, Craig D, McGuinness B, Todd S, Holmes C, Mann D, Smith AD, Beaumont H, Warden D, Wilcock G, Love S, Kehoe PG, Hooper NM, Vardy ER, Hardy J, Mead S, Fox NC, Rossor M, Collinge J, Maier W, Jessen F, Ruther E, Schurmann B, Heun R, Kolsch H, van den Bussche H, Heuser I, Kornhuber J, Wiltfang J, Dichgans M, Frolich L, Hampel H, Gallacher J, Hull M, Rujescu D, Giegling I, Goate AM, Kauwe JSK, Cruchaga C, Nowotny P, Morris JC, Mayo K, Sleegers K, Bettens K, Engelborghs S, De Deyn PP, Van Broeckhoven C, Livingston G, Bass NJ, Gurling H, McQuillin A, Gwilliam R, Deloukas P, Al-Chalabi A, Shaw CE, Tsolaki M, Singleton AB, Guerreiro R, Muhleisen TW, Nothen MM, Moebus S, Jockel KH, Klopp N, Wichmann HE, Pankratz VS, Sando SB, Aasly JO, Barcikowska M, Wszolek ZK, Dickson DW, Graff-Radford NR, Petersen RC, van Duijn CM, Breteler MMB, Ikram MA, DeStefano AL, Fitzpatrick AL, Lopez O, Launer LJ, Seshadri S, Berr C, Campion D, Epelbaum J, Dartigues JF, Tzourio C, Alperovitch A, Lathrop M, Feulner TM, Friedrich P, Riehle C, Krawczak M, Schreiber S, Mayhaus M, Nicolhaus S, Wagenpfeil S, Steinberg S, Stefansson H, Stefansson K, Snaedal J, Bjornsson S, Jonsson PV, Chouraki V, Genier-Boley B, Hiltunen M, Soininen H, Combarros O, Zelenika D, Delepine M, Bullido MJ, Pasquier F, Mateo I, Frank-Garcia A, Porcellini E, Hanon O, Coto E, Alvarez V, Bosco P, Siciliano G, Mancuso M, Panza F, Solfrizzi V, Nacmias B, Sorbi S, Bossu P, Piccardi P, Arosio B, Annoni G, Seripa D, Pilotto A, Scarpini E, Galimberti D, Brice A, Hannequin D, Licastro F, Jones L, Holmans PA, Jonsson T, Riemenschneider M, Morgan K, Younkin SG, Owen MJ, O'Donovan M, Amouyel P and Williams J. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease. Nat Genet 2011 May; 43: 429-35.
52. Yu JT and Tan L. The Role of Clusterin in Alzheimer's Disease: Pathways, Pathogenesis, and Therapy. Mol Neurobiol 2012; 45: 314-326.
53. Youle RJ and Strasser A. The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 2008; 9: 47-59.
54. Thambisetty M, An Y, Kinsey A, Koka D, Saleem M, Guntert A, Kraut M, Ferrucci L, Davatzikos C, Lovestone S and Resnick SM. Plasma clusterin concentration is associated with longitudinal brain atrophy in mild cognitive impairment. Neuroimage 2012; 59: 212-217.
55. Sborgi L, Barrera-Vilarmau S, Obregon P and de Alba E. Characterization of a novel interaction between Bcl-2 members Diva and Harakiri. PLoS One 2010; 5: e15575.
56. Bis JC, DeCarli C, Smith AV, van der Lijn F, Crivello F, Fornage M, Debette S, Shulman JM, Schmidt H, Srikanth V, Schuur M, Yu L, Choi SH, Sigurdsson S, Verhaaren BFJ, DeStefano AL, Lambert JC, Jack CR, Struchalin M, Stankovich J, Ibrahim-Verbaas CA, Fleischman D, Zijdenbos A, den Heijer T, Mazoyer B, Coker LH, Enzinger C, Danoy P, Amin N, Arfanakis K, van Buchem MA, de Bruijn RF, Beiser A, Dufouil C, Huang J, Cavalieri M, Thomson R, Niessen WJ, Chibnik LB, Gislason GK, Hofman A, Pikula A, Amouyel P, Freeman KB, Phan TG, Oostra BA, Stein JL, Medland SE, Vasquez AA, Hibar DP, Wright MJ, Franke B, Martin NG, Thompson PM, Nalls MA, Uitterlinden AG, Au R, Elbaz A, Beare RJ, van Swieten JC, Lopez OL, Harris TB, Chouraki V, Breteler MMB, De Jager PL, Becker JT, Vernooij MW, Knopman D, Fazekas F, Wolf PA, van der Lugt A, Gudnason V, Longstreth WT, Brown MA, Bennett DA, van Duijn CM, Mosley TH, Schmidt R, Tzourio C, Launer LJ, Ikram MA and Seshadri S. Common variants at 12q14 and 12q24 are associated with hippocampal volume. Nature Genetics 2012; 44: 545-551.
57. Jehle AW, Gardai SJ, Li S, Linsel-Nitschke P, Morimoto K, Janssen WJ, Vandivier RW, Wang N, Greenberg S, Dale BM, Qin C, Henson PM and Tall AR. ATP-binding cassette transporter A7 enhances phagocytosis of apoptotic cells and associated ERK signaling in macrophages. J Cell Biol 2006; 174: 547-556.
58. Jenner P and Olanow CW. Understanding cell death in Parkinson's disease. Ann Neurol 1998; 44: S72-84.
59. International Parkinson Disease Genomics Consortium; Nalls MA, Plagnol V, Hernandez DG, Sharma M, Sheerin UM, Saad M, Simon-Sanchez J, Schulte C, Lesage S, Sveinbjornsdottir S, Stefansson K, Martinez M, Hardy J, Heutink P, Brice A, Gasser T, Singleton AB and Wood NW. Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies. Lancet 2011; 377: 641-649.
60. Xu J, Kao SY, Lee FJ, Song W, Jin LW and Yankner BA. Dopamine-dependent neurotoxicity of alpha-synuclein: a mechanism for selective neurodegeneration in Parkinson disease. Nat Med 2002; 8: 600-606.
61. Iaccarino C, Crosio C, Vitale C, Sanna G, Carri MT and Barone P. Apoptotic mechanisms in mutant LRRK2-mediated cell death. Hum Mol Genet 2007; 16: 1319-1326.
62. Tong Y, Yamaguchi H, Giaime E, Boyle S, Kopan R, Kelleher RJ 3rd and Shen J. Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of alpha-synuclein, and apoptotic cell death in aged mice. Proc Natl Acad Sci U S A 2010; 107: 9879-9884.
63. Qureshi HY and Paudel HK. Parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and alpha-synuclein mutations promote Tau protein phosphorylation at Ser262 and destabilize microtubule cytoskeleton in vitro. J Biol Chem 2011; 286: 5055-5068.
64. Johnson BN, Berger AK, Cortese GP and Lavoie MJ. The ubiquitin E3 ligase parkin regulates the proapoptotic function of Bax. Proc Natl Acad Sci U S A 2012; 109: 6283-6288.
65. Sureda FX, Junyent F, Verdaguer E, Auladell C, Pelegri C, Vilaplana J, Folch J, Canudas AM, Zarate CB, Palles M and Camins A. Antiapoptotic drugs: a therapautic strategy for the prevention of neurodegenerative diseases. Curr Pharm Des 2011; 17: 230-245.
66. Rohn TT. The role of caspases in Alzheimer's disease; potential novel therapeutic opportunities. Apoptosis 2010; 15: 1403-1409.
67. Tabares-Seisdedos R, Dumont N, Baudot A, Valderas JM, Climent J, Valencia A, Crespo-Facorro B, Vieta E, Gomez-Beneyto M, Martinez S and Rubenstein JL. No paradox, no progress: inverse cancer comorbidity in people with other complex diseases. Lancet Oncol 2011; 12: 604-608.
68. Holohan KN, Lahiri DK, Schneider BP, Foroud T and Saykin AJ. Functional microRNAs in Alzheimer's disease and cancer: differential regulation of common mechanisms and pathway. Front Genet 2012; 3: 323.
69. Lipinski MM, Zheng B, Lu T, Yan Z, Py BF, Ng A, Xavier RJ, Li C, Yankner BA, Scherzer CR and Yuan J. Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer's disease. Proc Natl Acad Sci U S A 2010; 107: 14164-14169.
70. Sidransky E and Lopez G. The link between the GBA gene and parkinsonism. Lancet Neurol 2012; 11: 986-998.
71. Cullen V, Sardi SP, Ng J, Xu YH, Sun Y, Tomlinson JJ, Kolodziej P, Kahn I, Saftig P, Woulfe J, Rochet JC, Glicksman MA, Cheng SH, Grabowski GA, Shihabuddin LS and Schlossmacher MG. Acid β-glucosidase mutants linked to gaucher disease, parkinson disease, and lewy body dementia alter α-synuclein processing. Ann Neurol 2011; 69: 940-953.
72. Yang DS, Kumar A, Stavrides P, Peterson J, Peterhoff CM, Pawlik M, Levy E, Cataldo AM and Nixon RA. Neuronal apoptosis and autophagy cross talk in aging PS/APP mice, a model of Alzheimer's disease. Am J Pathol 2008; 173: 665-681.
73. Kroemer G and Levine B. Autophagic cell death: the story of a misnomer. Nat Rev Mol Cell Biol 2008; 9: 1004-1010.
74. Harris H and Rubinsztein DC. Control of autophagy as a therapy for neurodegenerative disease. Nat Rev Neurol 2012; 8: 108-117.
75. Atamna H and Frey WH 2nd. Mechanisms of mitochondrial dysfunction and energy deficiency in Alzheimer's disease. Mitochondrion 2007; 7: 297-310.
76. De Strooper B and Scorrano L. Close encounter: mitochondria, endoplasmic reticulum and Alzheimer's disease. EMBO J 2012; 31: 4095-4097.
77. Chang S, ran Ma T, Miranda RD, Balestra ME, Mahley RW and Huang Y. Lipid- and receptor-binding regions of apolipoprotein E4 fragments act in concert to cause mitochondrial dysfunction and neurotoxicity. Proc Natl Acad Sci U S A 2005; 102: 18694-18699.
78. Bruck S, Huber TB, Ingham RJ, Kim K, Niederstrasser H, Allen PM, Pawson T, Cooper JA and Shaw AS. Identification of a novel inhibitory actin-capping protein binding motif in CD2-associated protein. J Biol Chem 2006; 281: 19196-19203.
79. DuBoff B, Gotz J and Feany MB. Tau promotes neurodegeneration via DRP1 mislocalization in vivo. Neuron 2012; 75: 618-632.
80. Iijima-Ando K, Sekiya M, Maruko-Otake A, Ohtake Y, Suzuki E, Lu B and Iijima KM. Loss of axonal mitochondria promotes tau-mediated neurodegeneration and Alzheimer's disease-related tau phosphorylation via PAR-1. PLoS Genet 2012; 8: e1002918.
81. Krstic D and Knuesel I. Deciphering the mechanism underlying late-onset Alzheimer disease. Nat Rev Neurol 2013; 9: 25-34.
82. Rupprecht R, Papadopoulos V, Rammes G, Baghai TC, Fan J, Akula N, Groyer G, Adams D and Schumacher M. Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders. Nat Rev Drug Discov 2010; 9: 971-988.
83. Caselli RJ, Dueck AC, Huentelman MJ, Lutz MW, Saunders AM, Reiman EM and Roses AD. Longitudinal modeling of cognitive aging and the TOMM40 effect. Alzheimers Dement 2012; 8: 490-495.
84. Henchcliffe C and Beal MF. Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis. Nat Clin Pract Neurol 2008; 4: 600-609.
85. Lesage S and Brice A. Role of mendelian genes in "sporadic" Parkinson's disease. Parkinsonism Relat Disord 2012; 18 Suppl 1: S66-70.
86. Palikaras K and Tavernarakis N. Mitophagy in neurodegeneration and aging. Front Genet 2012; 3: 297.
87. Liu S, Sawada T, Lee S, Yu W, Silverio G, Alapatt P, Millan I, Shen A, Saxton W, Kanao T, Takahashi R, Hattori N, Imai Y and Lu B. Parkinson's disease-associated kinase PINK1 regulates Miro protein level and axonal transport of mitochondria. PLoS Genet 2012; 8: e1002537.
88. Thomas KJ, McCoy MK, Blackinton J, Beilina A, van der Brug M, Sandebring A, Miller D, Maric D, Cedazo-Minguez A and Cookson MR. DJ-1 acts in parallel to the PINK1/parkin pathway to control mitochondrial function and autophagy. Hum Mol Genet 2011; 20: 40-50.
89. Langston JW, Ballard P, Tetrud JW and Irwin I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 1983; 219: 979-980.
90. Blesa J, Phani S, Jackson-Lewis V and Przedborski S. Classic and new animal models of Parkinson's disease. J Biomed Biotechnol 2012; 2012: 845618.
91. Jenner P. Parkinson's disease, pesticides and mitochondrial dysfunction. Trends Neurosci 2001; 24: 245-247.
92. Yan MH, Wang X and Zhu X. Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease. Free Radic Biol Med 2013 Sep; 62: 90-101.
93. Lin MT and Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 2006; 443: 787-795.
94. Squier TC. Oxidative stress and protein aggregation during biological aging. Exp Gerontol 2001; 36: 1539-1550.
95. Kim RH, Smith PD, Aleyasin H, Hayley S, Mount MP, Pownall S, Wakeham A, You-Ten AJ, Kalia SK, Horne P, Westaway D, Lozano AM, Anisman H, Park DS and Mak TW. Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress. Proc Natl Acad Sci U S A 2005; 102: 5215-5220.
96. Irrcher I, Aleyasin H, Seifert EL, Hewitt SJ, Chhabra S, Phillips M, Lutz AK, Rousseaux MWC, Bevilacqua L, Jahani-Asl A, Callaghan S, MacLaurin JG, Winklhofer KF, Rizzu P, Rippstein P, Kim RH, Chen CX, Fon EA, Slack RS, Harper ME, McBride HM, Mak TW and Park DS. Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics. Hum Mol Genet 2010 Oct 1; 19: 3734-46.
97. Wu ZC, Yu JT, Li Y and Tan L. Clusterin in Alzheimer's disease. Adv Clin Chem 2012; 56: 155-173.
98. Allen M, Zou F, Chai HS, Younkin CS, Miles R, Nair AA, Crook JE, Pankratz VS, Carrasquillo MM, Rowley CN, Nguyen T, Ma L, Malphrus KG, Bisceglio G, Ortolaza AI, Palusak R, Middha S, Maharjan S, Georgescu C, Schultz D, Rakhshan F, Kolbert CP, Jen J, Sando SB, Aasly JO, Barcikowska M, Uitti RJ, Wszolek ZK, Ross OA, Petersen RC, Graff-Radford NR, Dickson DW, Younkin SG and Ertekin-Taner N. Glutathione S-transferase omega genes in Alzheimer and Parkinson disease risk, age-at-diagnosis and brain gene expression: an association study with mechanistic implications. Mol Neurodegener 2012; 7: 13.
99. De Jager PL, Shulman JM, Chibnik LB, Keenan BT, Raj T, Wilson RS, Yu L, Leurgans SE, Tran D, Aubin C, Anderson CD, Biffi A, Corneveaux JJ, Huentelman MJ; Alzheimer's Disease Neuroimaging Initiative; Rosand J, Daly MJ, Myers AJ, Reiman EM, Bennett DA and Evans DA. A genome-wide scan for common variants affecting the rate of age-related cognitive decline. Neurobiol Aging 2012; 33: 1017, e1011-1015.
100. Bajaj A, Driver JA and Schernhammer ES. Parkinson's disease and cancer risk: a systematic review and meta-analysis. Cancer Causes Control 2010; 21: 697-707.
101. Driver JA, Beiser A, Au R, Kreger BE, Splansky GL, Kurth T, Kiel DP, Lu KP, Seshadri S and Wolf PA. Inverse association between cancer and Alzheimer's disease: results from the Framingham Heart Study. BMJ 2012; 344: e1442.
102. Devine MJ, Plun-Favreau H and Wood NW. Parkinson's disease and cancer: two wars, one front. Nat Rev Cancer 2011; 11: 812-823.
103. Tollervey JR, Wang Z, Hortobagyi T, Witten JT, Zarnack K, Kayikci M, Clark TA, Schweitzer AC, Rot G, Curk T, Zupan B, Rogelj B, Shaw CE and Ule J. Analysis of alternative splicing associated with aging and neurodegeneration in the human brain. Genome Res 2011; 21: 1572-1582.
104. Kraft C, Peter M and Hofmann K. Selective autophagy: ubiquitin-mediated recognition and beyond. Nat Cell Biol 2010; 12: 836-841.
105. Ferrari R, Hardy J and Momeni P. Frontotemporal dementia: from Mendelian genetics towards genome wide association studies. J Mol Neurosci 2011; 45: 500-515.
106. Simpson JE, Ince PG, Shaw PJ, Heath PR, Raman R, Garwood CJ, Gelsthorpe C, Baxter L, Forster G, Matthews FE, Brayne C, Wharton SB; MRC Cognitive Function and Ageing Neuropathology Study Group. Microarray analysis of the astrocyte transcriptome in the aging brain: relationship to Alzheimer's pathology and APOE genotype. Neurobiol Aging 2011; 32: 1795-1807.
107. Kopito RR and Ron D. Conformational disease. Nat Cell Biol 2000; 2: E207-209.
108. Scorrano L, Oakes SA, Opferman JT, Cheng EH, Sorcinelli MD, Pozzan T and Korsmeyer SJ. BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis. Science 2003; 300: 135-139.
109. Smith DL, Pozueta J, Gong B, Arancio O and Shelanski M. Reversal of long-term dendritic spine alterations in Alzheimer disease models. Proc Natl Acad Sci U S A 2009; 106: 16877-16882.
110. Gong B, Cao Z, Zheng P, Vitolo OV, Liu S, Staniszewski A, Moolman D, Zhang H, Shelanski M and Arancio O. Ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory. Cell 2006; 126: 775-788.
111. Khandelwal PJ, Herman AM, Hoe HS, Rebeck GW and Moussa CE. Parkin mediates beclin-dependent autophagic clearance of defective mitochondria and ubiquitinated Abeta in AD models. Hum Mol Genet 2011; 20: 2091-2102.
112. Huynh DP, Scoles DR, Nguyen D and Pulst SM. The autosomal recessive juvenile Parkinson disease gene product, parkin, interacts with and ubiquitinates synaptotagmin XI. Hum Mol Genet 2003; 12: 2587-2597.
113. Rana A, Rera M and Walker DW. Parkin overexpression during aging reduces proteotoxicity, alters mitochondrial dynamics, and extends lifespan. Proc Natl Acad Sci U S A 2013; 110: 8638-8643.
114. Horwitz AR. The origins of the molecular era of adhesion research. Nat Rev Mol Cell Biol 2012; 13: 805-811.
115. Blalock EM, Geddes JW, Chen KC, Porter NM, Markesbery WR and Landfield PW. Incipient Alzheimer's disease: microarray correlation analyses reveal major transcriptional and tumor suppressor responses. Proc Natl Acad Sci U S A 2004; 101: 2173-2178.
116. Grunblatt E, Mandel S, Jacob-Hirsch J, Zeligson S, Amariglo N, Rechavi G, Li J, Ravid R, Roggendorf W, Riederer P and Youdim MB. Gene expression profiling of parkinsonian substantia nigra pars compacta; alterations in ubiquitin-proteasome, heat shock protein, iron and oxidative stress regulated proteins, cell adhesion/cellular matrix and vesicle trafficking genes. J Neural Transm 2004; 111: 1543-1573.
117. Miller RM, Kiser GL, Kaysser-Kranich TM, Lockner RJ, Palaniappan C and Federoff HJ. Robust dysregulation of gene expression in substantia nigra and striatum in Parkinson's disease. Neurobiol Dis 2006; 21: 305-313.
118. Xu PT, Li YJ, Qin XJ, Scherzer CR, Xu H, Schmechel DE, Hulette CM, Ervin J, Gullans SR, Haines J, Pericak-Vance MA and Gilbert JR. Differences in apolipoprotein E3/3 and E4/4 allele-specific gene expression in hippocampus in Alzheimer disease. Neurobiol Dis 2006; 21: 256-275.
119. Durakoglugil MS, Chen Y, White CL, Kavalali ET and Herz J. Reelin signaling antagonizes beta-amyloid at the synapse. Proc Natl Acad Sci U S A 2009; 106: 15938-15943.
120. Chen Y, Durakoglugil MS, Xian X and Herz J. ApoE4 reduces glutamate receptor function and synaptic plasticity by selectively impairing ApoE receptor recycling. Proc Natl Acad Sci U S A 2010; 107: 12011-12016.
121. Herring A, Donath A, Steiner KM, Widera MP, Hamzehian S, Kanakis D, Kolble K, ElAli A, Hermann DM, Paulus W and Keyvani K. Reelin depletion is an early phenomenon of Alzheimer's pathology. J Alzheimers Dis 2012; 30: 963-979.
122. Kramer PL, Xu H, Woltjer RL, Westaway SK, Clark D, Erten-Lyons D, Kaye JA, Welsh-Bohmer KA, Troncoso JC, Markesbery WR, Petersen RC, Turner RS, Kukull WA, Bennett DA, Galasko D, Morris JC and Ott J. Alzheimer disease pathology in cognitively healthy elderly: a genome-wide study. Neurobiol Aging 2011; 32: 2113-2122.
123. Kopan R and Ilagan MX. Gamma-secretase: proteasome of the membrane? Nat Rev Mol Cell Biol 2004; 5: 499-504.
124. Chen KP and Dou F. Selective interaction of amyloid precursor protein with different isoforms of neural cell adhesion molecule. J Mol Neurosci 2012; 46: 203-209.
125. Wang Y, West JD, MaGee TR, Mcdonald BC, Risacher SL, Shen L, Ramanan VK, Kim S, O'Neill DP, Farlow MR, Ghetti B and Saykin AJ. Hippocampal subfield atrophy on 3T MRI in prodromal Alzheimer's disease and older adults with cognitive complaints. Poster Presentation, Alzheimer's Association International Conference (AAIC) in Vancouver, British Colombia, Canada, July 14-19, 2012. 2012.
126. Saykin AJ, Shen L, Foroud TM, Potkin SG, Swaminathan S, Kim S, Risacher SL, Nho K, Huentelman MJ, Craig DW, Thompson PM, Stein JL, Moore JH, Farrer LA, Green RC, Bertram L, Jack CR Jr, Weiner MW; Alzheimer's Disease Neuroimaging Initiative. Alzheimer's Disease Neuroimaging Initiative biomarkers as quantitative phenotypes: Genetics core aims, progress, and plans. Alzheimers Dement 2010; 6: 265-273.
127. Edwards YJ, Beecham GW, Scott WK, Khuri S, Bademci G, Tekin D, Martin ER, Jiang Z, Mash DC, ffrench-Mullen J, Pericak-Vance MA, Tsinoremas N and Vance JM. Identifying consensus disease pathways in Parkinson's disease using an integrative systems biology approach. PLoS One 2011; 6: e16917.
128. Liu G, Jiang Y, Wang P, Feng R, Jiang N, Chen X, Song H and Chen Z. Cell adhesion molecules contribute to Alzheimer's disease: multiple pathway analyses of two genome-wide association studies. J Neurochem 2012; 120: 190-198.
129. Holmans P. Statistical methods for pathway analysis of genome-wide data for association with complex genetic traits. Adv Genet 2010; 72: 141-179.
130. Zhang M. Endocytic mechanisms and drug discovery in neurodegenerative diseases. Front Biosci 2008; 13: 6086-6105.
131. Jiang Q, Lee CY, Mandrekar S, Wilkinson B, Cramer P, Zelcer N, Mann K, Lamb B, Willson TM, Collins JL, Richardson JC, Smith JD, Comery TA, Riddell D, Holtzman DM, Tontonoz P and Landreth GE. ApoE promotes the proteolytic degradation of Abeta. Neuron 2008; 58: 681-693.
132. Pottier C, Hannequin D, Coutant S, Rovelet-Lecrux A, Wallon D, Rousseau S, Legallic S, Paquet C, Bombois S, Pariente J, Thomas-Anterion C, Michon A, Croisile B, Etcharry-Bouyx F, Berr C, Dartigues JF, Amouyel P, Dauchel H, Boutoleau-Bretonniere C, Thauvin C, Frebourg T, Lambert JC, Campion D and Collaborators PG. High frequency of potentially pathogenic SORL1 mutations in autosomal dominant early-onset Alzheimer disease. Mol Psychiatry 2012; 17: 875-879.
133. Reitz C, Cheng R, Rogaeva E, Lee JH, Tokuhiro S, Zou F, Bettens K, Sleegers K, Tan EK, Kimura R, Shibata N, Arai H, Kamboh MI, Prince JA, Maier W, Riemenschneider M, Owen M, Harold D, Hollingworth P, Cellini E, Sorbi S, Nacmias B, Takeda M, Pericak-Vance MA, Haines JL, Younkin S, Williams J, van Broeckhoven C, Farrer LA, St George-Hyslop PH, Mayeux R; Genetic and Environmental Risk in Alzheimer Disease 1 Consortium. Meta-analysis of the association between variants in SORL1 and Alzheimer disease. Arch Neurol 2011; 68: 99-106.
134. Rogaeva E, Meng Y, Lee JH, Gu Y, Kawarai T, Zou F, Katayama T, Baldwin CT, Cheng R, Hasegawa H, Chen F, Shibata N, Lunetta KL, Pardossi-Piquard R, Bohm C, Wakutani Y, Cupples LA, Cuenco KT, Green RC, Pinessi L, Rainero I, Sorbi S, Bruni A, Duara R, Friedland RP, Inzelberg R, Hampe W, Bujo H, Song YQ, Andersen OM, Willnow TE, Graff-Radford N, Petersen RC, Dickson D, Der SD, Fraser PE, Schmitt-Ulms G, Younkin S, Mayeux R, Farrer LA and St George-Hyslop P. The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nat Genet 2007; 39: 168-177.
135. Golde TE, Estus S, Younkin LH, Selkoe DJ and Younkin SG. Processing of the amyloid protein precursor to potentially amyloidogenic derivatives. Science 1992; 255: 728-730.
136. Alegre-Abarrategui J and Wade-Martins R. Parkinson disease, LRRK2 and the endocytic-autophagic pathway. Autophagy 2009; 5: 1208-1210.
137. Alegre-Abarrategui J, Christian H, Lufino MM, Mutihac R, Venda LL, Ansorge O and Wade-Martins R. LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. Hum Mol Genet 2009; 18: 4022-4034.
138. Matta S, Van Kolen K, da Cunha R, van den Bogaart G, Mandemakers W, Miskiewicz K, De Bock PJ, Morais VA, Vilain S, Haddad D, Delbroek L, Swerts J, Chavez-Gutierrez L, Esposito G, Daneels G, Karran E, Holt M, Gevaert K, Moechars DW, De Strooper B and Verstreken P. LRRK2 controls an EndoA phosphorylation cycle in synaptic endocytosis. Neuron 2012; 75: 1008-1021.
139. Cramer PE, Cirrito JR, Wesson DW, Lee CYD, Karlo JC, Zinn AE, Casali BT, Restivo JL, Goebel WD, James MJ, Brunden KR, Wilson DA and Landreth GE. ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models. Science 2012 Mar 23; 335: 1503-6.
140. Treusch S, Hamamichi S, Goodman JL, Matlack KES, Chung CY, Baru V, Shulman JM, Parrado A, Bevis BJ, Valastyan JS, Han H, Lindhagen-Persson M, Reiman EM, Evans DA, Bennett DA, Olofsson A, DeJager PL, Tanzi RE, Caldwell KA, Caldwell GA and Lindquist S. Functional Links Between Aβ Toxicity, Endocytic Trafficking, and Alzheimer's Disease Risk Factors in Yeast. Science 2011 Dec 2; 334: 1241-5.
141. Lee DW, Zhao X, Zhang F, Eisenberg E and Greene LE. Depletion of GAK/auxilin 2 inhibits receptor-mediated endocytosis and recruitment of both clathrin and clathrin adaptors. J Cell Sci 2005; 118: 4311-4321.
142. Dumitriu A, Pacheco CD, Wilk JB, Strathearn KE, Latourelle JC, Goldwurm S, Pezzoli G, Rochet JC, Lindquist S and Myers RH. Cyclin-G-associated kinase modifies alpha-synuclein expression levels and toxicity in Parkinson's disease: results from the GenePD Study. Hum Mol Genet 2011; 20: 1478-1487.
143. Henderson DM and Conner SD. A novel AAK1 splice variant functions at multiple steps of the endocytic pathway. Mol Biol Cell 2007; 18: 2698-2706.
144. Latourelle JC, Pankratz N, Dumitriu A, Wilk JB, Goldwurm S, Pezzoli G, Mariani CB, DeStefano AL, Halter C, Gusella JF, Nichols WC, Myers RH, Foroud T; PROGENI Investigators, Coordinators and Molecular Genetic Laboratories; GenePD Investigators, Coordinators and Molecular Genetic Laboratories. Genomewide association study for onset age in Parkinson disease. BMC Med Genet 2009; 10: 98.
145. Davies P and Maloney AJ. Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet 1976; 2: 1403.
146. Hoehn MM and Yahr MD. Parkinsonism: onset, progression and mortality. Neurology 1967; 17: 427-442.
147. Edwards RH. Neural degeneration and the transport of neurotransmitters. Ann Neurol 1993; 34: 638-645.
148. Corbett A, Pickett J, Burns A, Corcoran J, Dunnett SB, Edison P, Hagan JJ, Holmes C, Jones E, Katona C, Kearns I, Kehoe P, Mudher A, Passmore A, Shepherd N, Walsh F and Ballard C. Drug repositioning for Alzheimer's disease. Nat Rev Drug Discov 2012; 11: 833-846.
149. Antonini A and Albin RL. Dopaminergic treatment and nonmotor features of Parkinson disease: The horse lives. Neurology 2013; 80: 784-785.
150. Ho A and Shen J. Presenilins in synaptic function and disease. Trends Mol Med 2011; 17: 617-624.
151. Sweatt JD. Mechanisms of Memory. 2nd Edition. Academic Press, 2009.
152. Wu K, O'Keeffe D, Politis M, O'Keeffe GC, Robbins TW, Bose SK, Brooks DJ, Piccini P and Barker RA. The catechol-O-methyltransferase Val(158)Met polymorphism modulates fronto-cortical dopamine turnover in early Parkinson's disease: a PET study. Brain 2012; 135: 2449-2457.
153. Serretti A and Olgiati P. Catechol-o-methyltransferase and Alzheimer's disease: a review of biological and genetic findings. CNS Neurol Disord Drug Targets 2012; 11: 299-305.
154. Spence RD and Voskuhl RR. Neuroprotective effects of estrogens and androgens in CNS inflammation and neurodegeneration. Front Neuroendocrinol 2012; 33: 105-115.
155. Goldstein M and Lieberman A. The role of the regulatory enzymes of catecholamine synthesis in Parkinson's disease. Neurology 1992; 42: 8-12; discussion 41-18.
156. Gainetdinov RR, Fumagalli F, Jones SR and Caron MG. Dopamine transporter is required for in vivo MPTP neurotoxicity: evidence from mice lacking the transporter. J Neurochem 1997; 69: 1322-1325.
157. Baranzini SE, Srinivasan R, Khankhanian P, Okuda DT, Nelson SJ, Matthews PM, Hauser SL, Oksenberg JR and Pelletier D. Genetic variation influences glutamate concentrations in brains of patients with multiple sclerosis. Brain 2010; 133: 2603-2611.
158. Mayeux R. Clinical practice. Early Alzheimer's disease. N Engl J Med 2010; 362: 2194-2201.
159. Alkalay A, Rabinovici GD, Zimmerman G, Agarwal N, Kaufer D, Miller BL, Jagust WJ and Soreq H. Plasma acetylchol inesterase activity correlates with intracerebral beta-amyloid load. Curr Alzheimer Res 2013; 10: 48-56.
160. Ramanan VK, Risacher SL, Nho K, Kim S, Swaminathan S, Shen L, Foroud TM, Hakonarson H, Huentelman MJ, Aisen PS, Petersen RC, Green RC, Jack CR, Koeppe RA, Jagust WJ, Weiner MW and Saykin AJ. APOE and BCHE as modulators of cerebral amyloid deposition: a florbetapir PET genome-wide association study. Mol Psychiatry 2013 Feb 19; [Epub ahead of print].
161. Mesulam MM and Geula C. Butyrylchol inesterase reactivity differentiates the amyloid plaques of aging from those of dementia. Ann Neurol 1994; 36: 722-727.
162. Darvesh S, Hopkins DA and Geula C. Neurobiology of butyrylchol inesterase. Nat Rev Neurosci 2003; 4: 131-138.
163. Darreh-Shori T, Forsberg A, Modiri N, Andreasen N, Blennow K, Kamil C, Ahmed H, Almkvist O, Långström B and Nordberg A. Differential levels of apolipoprotein E and butyrylcho-linesterase show strong association with pathological signs of Alzheimer's disease in the brain in vivo. Neurobiol Aging 2011 Dec; 32: 2320, e15-32.
164. Darvesh S, Cash MK, Reid GA, Martin E, Mitnitski A and Geula C. Butyrylchol inesterase is associated with beta-amyloid plaques in the transgenic APPSWE/PSEN1dE9 mouse model of Alzheimer disease. J Neuropathol Exp Neurol 2012; 71: 2-14.
165. Lane RM and He Y. Butyrylchol inesterase genotype and gender influence Alzheimer's disease phenotype. Alzheimers Dement 2013 Mar; 9: e1-73.
166. Sabbagh MN, Farlow MR, Relkin N and Beach TG. Do cholinergic therapies have disease-modifying effects in Alzheimer's disease? Alzheimers Dement 2006 Apr; 2: 118-25.
167. Farlow MR, Miller ML and Pejovic V. Treatment options in Alzheimer's disease: maximizing benefit, managing expectations. Dement Geriatr Cogn Disord 2008; 25: 408-422.
168. Caughey B and Baron GS. Prions and their partners in crime. Nature 2006; 443: 803-810.
169. Prusiner SB. Scrapie prions. Annu Rev Microbiol 1989; 43: 345-374.
170. Prusiner SB. Cell biology. A unifying role for prions in neurodegenerative diseases. Science 2012; 336: 1511-1513.
171. Dermaut B, Croes EA, Rademakers R, Van den Broeck M, Cruts M, Hofman A, van Duijn CM and Van Broeckhoven C. PRNP Val129 homozygosity increases risk for early-onset Alzheimer's disease. Ann Neurol 2003; 53: 409-412.
172. Riemenschneider M, Klopp N, Xiang W, Wagenpfeil S, Vollmert C, Muller U, Forstl H, Illig T, Kretzschmar H and Kurz A. Prion protein codon 129 polymorphism and risk of Alzheimer disease. Neurology 2004; 63: 364-366.
173. Gossrau G, Herting B, Mockel S, Kempe A, Koch R, Reichmann H and Lampe JB. Analysis of the polymorphic prion protein gene codon 129 in idiopathic Parkinson's disease. J Neural Transm 2006; 113: 331-337.
174. Combarros O, Sanchez-Guerra M, Llorca J, Alvarez-Arcaya A, Berciano J, Pena N and Fernandez-Viadero C. Polymorphism at codon 129 of the prion protein gene is not associated with sporadic AD. Neurology 2000; 55: 593-595.
175. Jeong BH, Lee KH, Lee YJ, Kim Y, Choi EK, Kim YH, Cho YS, Carp R and Kim YS. Lack of association between PRNP 1368 polymorphism and Alzheimer's disease or vascular dementia. BMC Med Genet 2009; 10: 32.
176. Mead S, Poulter M, Uphill J, Beck J, Whitfield J, Webb TEF, Campbell T, Adamson G, Deriziotis P, Tabrizi SJ, Hummerich H, Verzilli C, Alpers MP, Whittaker JC and Collinge J. Genetic risk factors for variant Creutzfeldt-Jakob disease: a genome-wide association study. Lancet Neurol 2009; 8: 57-66.
177. Mead S, Uphill J, Beck J, Poulter M, Campbell T, Lowe J, Adamson G, Hummerich H, Klopp N, Rückert IM, Wichmann HE, Azazi D, Plagnol V, Pako WH, Whitfield J, Alpers MP, Whittaker J, Balding DJ, Zerr I, Kretzschmar H and Collinge J. Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP. Hum Mol Genet 2012 Apr 15; 21: 1897-906.
178. Lukic A and Mead S. Genome wide association studies and prion disease. Prion 2011; 5: 154-160.
179. Lansbury PT and Lashuel HA. A century-old debate on protein aggregation and neurodegeneration enters the clinic. Nature 2006; 443: 774-779.
180. Swardfager W, Lanctot K, Rothenburg L, Wong A, Cappell J and Herrmann N. A meta-analysis of cytokines in Alzheimer's disease. Biol Psychiatry 2010; 68: 930-941.
181. Akama KT and Van Eldik LJ. Beta-amyloid stimulation of inducible nitric-oxide synthase in astrocytes is interleukin-1beta- and tumor necrosis factor-alpha (TNFalpha)-dependent, and involves a TNFalpha receptor-associated factor- and NFkappaB-inducing kinase-dependent signaling mechanism. J Biol Chem 2000; 275: 7918-7924.
182. Blum-Degen D, Muller T, Kuhn W, Gerlach M, Przuntek H and Riederer P. Interleukin-1 beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer's and de novo Parkinson's disease patients. Neurosci Lett 1995; 202: 17-20.
183. Hirsch EC and Hunot S. Neuroinflammation in Parkinson's disease: a target for neuroprotection? Lancet Neurol 2009; 8: 382-397.
184. Stewart WF, Kawas C, Corrada M and Metter EJ. Risk of Alzheimer's disease and duration of NSAID use. Neurology 1997; 48: 626-632.
185. Wahner AD, Bronstein JM, Bordelon YM and Ritz B. Nonsteroidal anti-inflammatory drugs may protect against Parkinson disease. Neurology 2007; 69: 1836-1842.
186. Prinz M, Priller J, Sisodia SS and Ransohoff RM. Heterogeneity of CNS myeloid cells and their roles in neurodegeneration. Nat Neurosci 2011; 14: 1227-1235.
187. Lucin KM and Wyss-Coray T. Immune activation in brain aging and neurodegeneration: too much or too little? Neuron 2009; 64: 110-122.
188. Lee EJ, Woo MS, Moon PG, Baek MC, Choi IY, Kim WK, Junn E and Kim HS. α-Synuclein Activates Microglia by Inducing the Expressions of Matrix Metalloproteinases and the Subsequent Activation of Protease-Activated Receptor-1. J Immunol 2010 Jul 1; 185: 615-23.
189. Halle A, Hornung V, Petzold GC, Stewart CR, Monks BG, Reinheckel T, Fitzgerald KA, Latz E, Moore KJ and Golenbock DT. The NALP3 inflammasome is involved in the innate immune response to amyloid-[beta]. Nat Immunol 2008; 9: 857-865.
190. Kitazawa M, Cheng D, Tsukamoto MR, Koike MA, Wes PD, Vasilevko V, Cribbs DH and LaFerla FM. Blocking IL-1 Signaling Rescues Cognition, Attenuates Tau Pathology, and Restores Neuronal β-Catenin Pathway Function in an Alzheimer's Disease Model. J Immunol 2011 Dec 15; 187: 6539-49.
191. Pott Godoy MC, Tarelli R, Ferrari CC, Sarchi MI and Pitossi FJ. Central and systemic IL-1 exacerbates neurodegeneration and motor symptoms in a model of Parkinson's disease. Brain 2008; 131: 1880-1894.
192. Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S, Vieira-Saecker A, Griep A, Axt D, Remus A, Tzeng TC, Gelpi E, Halle A, Korte M, Latz E and Golenbock DT. NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature 2013; 493: 674-678.
193. White GE and Greaves DR. Fractalkine: a survivor's guide: chemokines as antiapoptotic mediators. Arterioscler Thromb Vasc Biol 2012; 32: 589-594.
194. Cardona AE, Pioro EP, Sasse ME, Kostenko V, Cardona SM, Dijkstra IM, Huang D, Kidd G, Dombrowski S, Dutta R, Lee JC, Cook DN, Jung S, Lira SA, Littman DR and Ransohoff RM. Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci 2006; 9: 917-924.
195. Bamberger ME, Harris ME, McDonald DR, Husemann J and Landreth GE. A cell surface receptor complex for fibrillar beta-amyloid mediates microglial activation. J Neurosci 2003; 23: 2665-2674.
196. El Khoury J, Toft M, Hickman SE, Means TK, Terada K, Geula C and Luster AD. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat Med 2007; 13: 432-438.
197. Heneka MT, Nadrigny F, Regen T, Martinez-Hernandez A, Dumitrescu-Ozimek L, Terwel D, Jardanhazi-Kurutz D, Walter J, Kirchhoff F, Hanisch UK and Kummer MP. Locus ceruleus controls Alzheimer's disease pathology by modulating microglial functions through norepinephrine. Proc Natl Acad Sci U S A 2010; 107: 6058-6063.
198. Ramos EM, Lin MT, Larson EB, Maezawa I, Tseng LH, Edwards KL, Schellenberg GD, Hansen JA, Kukull WA and Jin LW. Tumor necrosis factor alpha and interleukin 10 promoter region polymorphisms and risk of late-onset Alzheimer disease. Arch Neurol 2006; 63: 1165-1169.
199. Wahner AD, Sinsheimer JS, Bronstein JM and Ritz B. Inflammatory cytokine gene polymorphisms and increased risk of Parkinson disease. Arch Neurol 2007; 64: 836-840.
200. Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, Cruchaga C, Sassi C, Kauwe JS, Younkin S, Hazrati L, Collinge J, Pocock J, Lashley T, Williams J, Lambert JC, Amouyel P, Goate A, Rademakers R, Morgan K, Powell J, St George-Hyslop P, Singleton A, Hardy J; Alzheimer Genetic Analysis Group. TREM2 variants in Alzheimer's disease. N Engl J Med 2013; 368: 117-127.
201. Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson PV, Snaedal J, Bjornsson S, Huttenlocher J, Levey AI, Lah JJ, Rujescu D, Hampel H, Giegling I, Andreassen OA, Engedal K, Ulstein I, Djurovic S, Ibrahim-Verbaas C, Hofman A, Ikram MA, van Duijn CM, Thorsteinsdottir U, Kong A and Stefansson K. Variant of TREM2 associated with the risk of Alzheimer's disease. N Engl J Med 2013; 368: 107-116.
202. Hamerman JA, Jarjoura JR, Humphrey MB, Nakamura MC, Seaman WE and Lanier LL. Cutting edge: inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12. J Immunol 2006; 177: 2051-2055.
203. Turnbull IR, Gilfillan S, Cella M, Aoshi T, Miller M, Piccio L, Hernandez M and Colonna M. Cutting edge: TREM-2 attenuates macrophage activation. J Immunol 2006; 177: 3520-3524.
204. Zhang B, Gaiteri C, Bodea LG, Wang Z, McElwee J, Podtelezhnikov AA, Zhang C, Xie T, Tran L, Dobrin R, Fluder E, Clurman B, Melquist S, Narayanan M, Suver C, Shah H, Mahajan M, Gillis T, Mysore J, MacDonald ME, Lamb JR, Bennett DA, Molony C, Stone DJ, Gudnason V, Myers AJ, Schadt EE, Neumann H, Zhu J and Emilsson V. Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer's disease. Cell 2013; 153: 707-720.
205. Moehle MS, Webber PJ, Tse T, Sukar N, Standaert DG, DeSilva TM, Cowell RM and West AB. LRRK2 inhibition attenuates microglial inflammatory responses. J Neurosci 2012; 32: 1602-1611.
206. Kim B, Yang MS, Choi D, Kim JH, Kim HS, Seol W, Choi S, Jou I, Kim EY and Joe EH. Impaired inflammatory responses in murine Lrrk2-knockdown brain microglia. PLoS One 2012; 7: e34693.
207. Gardet A, Benita Y, Li C, Sands BE, Ballester I, Stevens C, Korzenik JR, Rioux JD, Daly MJ, Xavier RJ and Podolsky DK. LRRK2 Is Invol-ved in the IFN-γ Response and Host Response to Pathogens. J Immunol 2010; 185: 5577-5585.
208. Jun G, Naj AC, Beecham GW, Wang LS, Buros J, Gallins PJ, Buxbaum JD, Ertekin-Taner N, Fallin MD, Friedland R, Inzelberg R, Kramer P, Rogaeva E, St George-Hyslop P, Arnold SE, Baldwin CT, Barber R, Beach T, Bigio EH, Bird TD, Boxer A, Burke JR, Cairns N, Carroll SL, Chui HC, Clark DG, Cotman CW, Cummings JL, DeCarli C, Diaz-Arrastia R, Dick M, Dickson DW, Ellis WG, Fallon KB, Farlow MR, Ferris S, Frosch MP, Galasko DR, Gearing M, Geschwind DH, Ghetti B, Gilman S, Giordani B, Glass J, Graff-Radford NR, Green RC, Growdon JH, Hamilton RL, Harrell LE, Head E, Honig LS, Hulette CM, Hyman BT, Jicha GA, Jin LW, Johnson N, Karlawish J, Karydas A, Kaye JA, Kim R, Koo EH, Kowall NW, Lah JJ, Levey AI, Lieberman A, Lopez OL, Mack WJ, Markesbery W, Marson DC, Martiniuk F, Masliah E, McKee AC, Mesulam M, Miller JW, Miller BL, Miller CA, Parisi JE, Perl DP, Peskind E, Petersen RC, Poon W, Quinn JF, Raskind M, Reisberg B, Ringman JM, Roberson ED, Rosenberg RN, Sano M, Schneider JA, Schneider LS, Seeley W, Shelanski ML, Smith CD, Spina S, Stern RA, Tanzi RE, Trojanowski JQ, Troncoso JC, Van Deerlin VM, Vinters HV, Vonsattel JP, Weintraub S, Welsh-Bohmer KA, Woltjer RL, Younkin SG, Cantwell LB, Dombroski BA, Saykin AJ, Reiman EM, Bennett DA, Morris JC, Lunetta KL, Martin ER, Montine TJ, Goate AM, Blacker D, Tsuang DW, Beekly D, Cupples LA, Hakonarson H, Kukull W, Foroud TM, Haines J, Mayeux R, Farrer LA, Pericak-Vance MA, Schellenberg GD; Alzheimer's Disease Genetics Consortium. Meta-analysis Confirms CR1, CLU, and PICALM as Alzheimer Disease Risk Loci and Reveals Interactions With APOE Genotypes. Arch Neurol 2010; 67: 1473-1484.
209. Chibnik LB, Shulman JM, Leurgans SE, Schneider JA, Wilson RS, Tran D, Aubin C, Buchman AS, Heward CB, Myers AJ, Hardy JA, Huentelman MJ, Corneveaux JJ, Reiman EM, Evans DA, Bennett DA and De Jager PL. CR1 is associated with amyloid plaque burden and age-related cognitive decline. Ann Neurol 2011; 69: 560-569.
210. Wijsman EM, Pankratz ND, Choi Y, Rothstein JH, Faber KM, Cheng R, Lee JH, Bird TD, Bennett DA, Diaz-Arrastia R, Goate AM, Farlow M, Ghetti B, Sweet RA, Foroud TM, Mayeux R; NIA-LOAD/NCRAD Family Study Group. Genome-Wide Association of Familial Late-Onset Alzheimer's Disease Replicates BIN1 and CLU and Nominates CUGBP2 in Interaction with APOE. PLoS Genet 2011; 7: e1001308.
211. Barral S, Bird T, Goate A, Farlow MR, Diaz-Arrastia R, Bennett DA, Graff-Radford N, Boeve BF, Sweet RA, Stern Y, Wilson RS, Foroud T, Ott J, Mayeux R; National Institute on Aging Late-Onset Alzheimer's Disease Genetics Study. Genotype patterns at PICALM, CR1, BIN1, CLU, and APOE genes are associated with episodic memory. Neurology 2012; 78: 1464-1471.
212. Keenan BT, Shulman JM, Chibnik LB, Raj T, Tran D, Sabuncu MR; Alzheimer's Disease Neuroimaging Initiative; Allen AN, Corneveaux JJ, Hardy JA, Huentelman MJ, Lemere CA, Myers AJ, Nicholson-Weller A, Reiman EM, Evans DA, Bennett DA, De Jager PL. A coding variant in CR1 interacts with APOE-epsilon4 to influence cognitive decline. Hum Mol Genet 2012; 21: 2377-2388.
213. Stephan AH, Barres BA and Stevens B. The complement system: an unexpected role in synaptic pruning during development and disease. Annu Rev Neurosci 2012; 35: 369-389.
214. Evans MC, Couch Y, Sibson N and Turner MR. Inflammation and neurovascular changes in amyotrophic lateral sclerosis. Mol Cell Neurosci 2013; 53: 34-41.
215. Yin F, Banerjee R, Thomas B, Zhou P, Qian L, Jia T, Ma X, Ma Y, Iadecola C, Beal MF, Nathan C and Ding A. Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice. J Exp Med 2010; 207: 117-128.
216. Jones KA and Thomsen C. The role of the innate immune system in psychiatric disorders. Mol Cell Neurosci 2013; 53: 52-62.
217. Vom Berg J, Prokop S, Miller KR, Obst J, Kalin RE, Lopategui-Cabezas I, Wegner A, Mair F, Schipke CG, Peters O, Winter Y, Becher B and Heppner FL. Inhibition of IL-12/IL-23 signaling reduces Alzheimer's disease-like pathology and cognitive decline. Nat Med 2012; 18: 1812-1819.
218. Gao HM, Liu B, Zhang W and Hong JS. Novel anti-inflammatory therapy for Parkinson's disease. Trends Pharmacol Sci 2003; 24: 395-401.
219. Tan ZS and Seshadri S. Inflammation in the Alzheimer's disease cascade: culprit or innocent bystander? Alzheimers Res Ther 2010; 2: 6.
220. Martins IJ, Hone E, Foster JK, Sunram-Lea SI, Gnjec A, Fuller SJ, Nolan D, Gandy SE and Martins RN. Apolipoprotein E, cholesterol metabolism, diabetes, and the convergence of risk factors for Alzheimer's disease and cardiovascular disease. Mol Psychiatry 2006; 11: 721-736.
221. Sparks DL. Alzheimer disease: statins in the treatment of Alzheimer disease. Nat Rev Neurol 2011; 7: 662-663.
222. Gao X, Simon KC, Schwarzschild MA and Ascherio A. Prospective study of statin use and risk of Parkinson disease. Arch Neurol 2012; 69: 380-384.
223. Karasinska JM and Hayden MR. Cholesterol metabolism in Huntington disease. Nat Rev Neurol 2011; 7: 561-572.
224. Anchisi L, Dessi S, Pani A and Mandas A. Cholesterol homeostasis: a key to prevent or slow down neurodegeneration. Front Physiol 2012; 3: 486.
225. Han X, Rozen S, Boyle SH, Hellegers C, Cheng H, Burke JR, Welsh-Bohmer KA, Doraiswamy PM and Kaddurah-Daouk R. Metabolomics in early Alzheimer's disease: identification of altered plasma sphingolipidome using shotgun lipidomics. PLoS One 2011; 6: e21643.
226. Wood PL. Lipidomics of Alzheimer's disease: current status. Alzheimers Res Ther 2012; 4: 5.
227. Holtzman DM, Herz J and Bu G. Apolipoprotein e and apolipoprotein e receptors: normal biology and roles in Alzheimer disease. Cold Spring Harb Perspect Med 2012; 2: a006312.
228. Calero M, Tokuda T, Rostagno A, Kumar A, Zlokovic B, Frangione B and Ghiso J. Functional and structural properties of lipid-associated apolipoprotein J (clusterin). Biochem J 1999; 344: 375-383.
229. Kim WS, Weickert CS and Garner B. Role of ATP-binding cassette transporters in brain lipid transport and neurological disease. J Neurochem 2008; 104: 1145-1166.
230. Soscia SJ and Fitzgerald ML. The ABCA7 transporter, brain lipids and Alzheimer's disease. Clinical Lipidology 2013; 8: 97-108.
231. Biskup S, Moore DJ, Celsi F, Higashi S, West AB, Andrabi SA, Kurkinen K, Yu SW, Savitt JM, Waldvogel HJ, Faull RL, Emson PC, Torp R, Ottersen OP, Dawson TM and Dawson VL. Localization of LRRK2 to membranous and vesicular structures in mammalian brain. Ann Neurol 2006; 60: 557-569.
232. Kim KY, Stevens MV, Akter MH, Rusk SE, Huang RJ, Cohen A, Noguchi A, Springer D, Bocharov AV, Eggerman TL, Suen DF, Youle RJ, Amar M, Remaley AT and Sack MN. Parkin is a lipid-responsive regulator of fat uptake in mice and mutant human cells. J Clin Invest 2011; 121: 3701-3712.
233. Hatano T, Kubo S, Imai S, Maeda M, Ishikawa K, Mizuno Y and Hattori N. Leucine-rich repeat kinase 2 associates with lipid rafts. Hum Mol Genet 2007; 16: 678-690.
234. Chan RB, Oliveira TG, Cortes EP, Honig LS, Duff KE, Small SA, Wenk MR, Shui G and Di Paolo G. Comparative lipidomic analysis of mouse and human brain with Alzheimer disease. J Biol Chem 2012; 287: 2678-2688.
235. Cheng D, Jenner AM, Shui G, Cheong WF, Mitchell TW, Nealon JR, Kim WS, McCann H, Wenk MR, Halliday GM and Garner B. Lipid pathway alterations in Parkinson's disease primary visual cortex. PLoS One 2011; 6: e17299.
236. Ho PP, Kanter JL, Johnson AM, Srinagesh HK, Chang EJ, Purdy TM, van Haren K, Wikoff WR, Kind T, Khademi M, Matloff LY, Narayana S, Hur EM, Lindstrom TM, He Z, Fiehn O, Olsson T, Han X, Han MH, Steinman L and Robinson WH. Identification of Naturally Occurring Fatty Acids of the Myelin Sheath That Resolve Neuroinflammation. Sci Transl Med 2012; 4: 137ra173.
237. Willey JZ and Elkind MS. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors in the treatment of central nervous system diseases. Arch Neurol 2010; 67: 1062-1067.
238. Kroner Z. The relationship between Alzheimer's disease and diabetes: type 3 diabetes? Altern Med Rev 2009; 14: 373-379.
239. Liu Y, Liu F, Grundke-Iqbal I, Iqbal K and Gong CX. Deficient brain insulin signalling pathway in Alzheimer's disease and diabetes. J Pathol 2011; 225: 54-62.
240. Vignini A, Giulietti A, Nanetti L, Raffaelli F, Giusti L, Mazzanti L and Provinciali L. Alzheimer's disease And Diabetes: New Insights and Unifying Therapies. Curr Diabetes Rev 2013 May; 9: 218-27.
241. de la Monte SM. Contributions of brain insulin resistance and deficiency in amyloid-related neurodegeneration in Alzheimer's disease. Drugs 2012; 72: 49-66.
242. Chen DY, Stern SA, Garcia-Osta A, Saunier-Rebori B, Pollonini G, Bambah-Mukku D, Blitzer RD and Alberini CM. A critical role for IGF-II in memory consolidation and enhancement. Nature 2011; 469: 491-497.
243. Lue LF, Andrade C, Sabbagh M and Walker D. Is There Inflammatory Synergy in Type II Diabetes Mellitus and Alzheimer's Disease? Int J Alzheimers Dis 2012; 2012: 918680.
244. Iwasaki T, Yoneda M, Nakajima A and Terauchi Y. Serum Butyrylchol inesterase is Strongly Associated with Adiposity, the Serum Lipid Profile and Insulin Resistance. Intern Med 2007; 46: 1633-9.
245. Meigs JB, Manning AK, Fox CS, Florez JC, Liu C, Cupples LA and Dupuis J. Genome-wide association with diabetes-related traits in the Framingham Heart Study. BMC Med Genet 2007; 8 Suppl 1: S16.
246. Gao C, Holscher C, Liu Y and Li L. GSK3: a key target for the development of novel treatments for type 2 diabetes mellitus and Alzheimer disease. Rev Neurosci 2012; 23: 1-11.
247. Akinyemi R, Mukaetova-Ladinska E, Attems J, Attems J, Ihara M and Kalaria RN. Vascular Risk Factors and Neurodegeneration in Ageing related Dementias: Alzheimer's Disease and Vascular Dementia. Curr Alzheimer Res 2013 Jul; 10: 642-53.
248. McCarron MO, Delong D and Alberts MJ. APOE genotype as a risk factor for ischemic cerebrovascular disease: a meta-analysis. Neurology 1999; 53: 1308-1311.
249. Desai BS, Monahan AJ, Carvey PM and Hendey B. Blood-brain barrier pathology in Alzheimer's and Parkinson's disease: implications for drug therapy. Cell Transplant 2007; 16: 285-299.
250. Chen X, Ghribi O and Geiger JD. Caffeine protects against disruptions of the blood-brain barrier in animal models of Alzheimer's and Parkinson's diseases. J Alzheimers Dis 2010; 20 Suppl 1: S127-141.
251. Bartels AL. Blood-brain barrier P-glycoprotein function in neurodegenerative disease. Curr Pharm Des 2011; 17: 2771-2777.
252. Silver M, Janousova E, Hua X, Thompson PM and Montana G. Identification of gene pathways implicated in Alzheimer's disease using longitudinal imaging phenotypes with sparse regression. Neuroimage 2012; 63: 1681-1694.
253. Biffi A, Shulman JM, Jagiella JM, Cortellini L, Ayres AM, Schwab K, Brown DL, Silliman SL, Selim M, Worrall BB, Meschia JF, Slowik A, De Jager PL, Greenberg SM, Schneider JA, Bennett DA and Rosand J. Genetic variation at CR1 increases risk of cerebral amyloid angiopathy. Neurology 2012; 78: 334-341.
254. Mihci E, Ozkaynak SS, Sallakci N, Kizilay F and Yavuzer U. VEGF polymorphisms and serum VEGF levels in Parkinson's disease. Neurosci Lett 2011; 494: 1-5.
255. He D, Lu W, Chang K, Liu Y, Zhang J and Zeng Z. Vascular endothelial growth factor polymorphisms and risk of Alzheimer's disease: a meta-analysis. Gene 2013; 518: 296-302.
256. Topiwala A and Ebmeier KP. Vascular changes and brain plasticity: a new approach to neurodegenerative diseases. Am J Neurodegener Dis 2012; 1: 152-159.
257. Alvarez JI, Dodelet-Devillers A, Kebir H, Ifergan I, Fabre PJ, Terouz S, Sabbagh M, Wosik K, Bourbonniere L, Bernard M, van Horssen J, de Vries HE, Charron F and Prat A. The Hedgehog pathway promotes blood-brain barrier integrity and CNS immune quiescence. Science 2011; 334: 1727-1731.
258. Schrijvers EM, Schurmann B, Koudstaal PJ, van den Bussche H, Van Duijn CM, Hentschel F, Heun R, Hofman A, Jessen F, Kolsch H, Kornhuber J, Peters O, Rivadeneira F, Ruther E, Uitterlinden AG, Riedel-Heller S, Dichgans M, Wiltfang J, Maier W, Breteler MM and Ikram MA. Genome-wide association study of vascular dementia. Stroke 2012; 43: 315-319.
259. Chuang DM, Leng Y, Marinova Z, Kim HJ and Chiu CT. Multiple roles of HDAC inhibition in neurodegenerative conditions. Trends Neurosci 2009; 32: 591-601.
260. Egger G, Liang G, Aparicio A and Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature 2004; 429: 457-463.
261. Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suner D, Cigudosa JC, Urioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, Ling C, Carlsson E, Poulsen P, Vaag A, Stephan Z, Spector TD, Wu YZ, Plass C and Esteller M. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A 2005; 102: 10604-10609.
262. Kontopoulos E, Parvin JD and Feany MB. Alpha-synuclein acts in the nucleus to inhibit histone acetylation and promote neurotoxicity. Hum Mol Genet 2006; 15: 3012-3023.
263. Outeiro TF, Kontopoulos E, Altmann SM, Kufareva I, Strathearn KE, Amore AM, Volk CB, Maxwell MM, Rochet JC, McLean PJ, Young AB, Abagyan R, Feany MB, Hyman BT and Kazantsev AG. Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease. Science 2007; 317: 516-519.
264. Graff J, Rei D, Guan JS, Wang WY, Seo J, Hennig KM, Nieland TJ, Fass DM, Kao PF, Kahn M, Su SC, Samiei A, Joseph N, Haggarty SJ, Delalle I and Tsai LH. An epigenetic blockade of cognitive functions in the neurodegenerating brain. Nature 2012; 483: 222-226.
265. Donmez G, Wang D, Cohen DE and Guarente L. SIRT1 suppresses beta-amyloid production by activating the alpha-secretase gene ADAM10. Cell 2010; 142: 320-332.
266. Beck J, Poulter M, Hensman D, Rohrer JD, Mahoney CJ, Adamson G, Campbell T, Uphill J, Borg A, Fratta P, Orrell RW, Malaspina A, Rowe J, Brown J, Hodges J, Sidle K, Polke JM, Houlden H, Schott JM, Fox NC, Rossor MN, Tabrizi SJ, Isaacs AM, Hardy J, Warren JD, Collinge J and Mead S. Large C9orf72 hexanucleotide repeat expansions are seen in multiple neurodegenerative syndromes and are more frequent than expected in the UK population. Am J Hum Genet 2013; 92: 345-353.
267. Mori K, Weng SM, Arzberger T, May S, Rentzsch K, Kremmer E, Schmid B, Kretzschmar HA, Cruts M, Van Broeckhoven C, Haass C and Edbauer D. The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALS. Science 2013; 339: 1335-1338.
268. Taylor JP. Neuroscience. RNA that gets RAN in neurodegeneration. Science 2013; 339: 1282-1283.
269. Rao JS, Keleshian VL, Klein S and Rapoport SI. Epigenetic modifications in frontal cortex from Alzheimer's disease and bipolar disorder patients. Transl Psychiatry 2012; 2: e132.
270. Chowdary PD, Che DL and Cui B. Neurotrophin signaling via long-distance axonal transport. Annu Rev Phys Chem 2012; 63: 571-594.
271. Schindowski K, Belarbi K and Buee L. Neurotrophic factors in Alzheimer's disease: role of axonal transport. Genes Brain Behav 2008; 7 Suppl 1: 43-56.
272. Kauwe JS, Wang J, Mayo K, Morris JC, Fagan AM, Holtzman DM and Goate AM. Alzheimer's disease risk variants show association with cerebrospinal fluid amyloid beta. Neurogenetics 2009; 10: 13-17.
273. Karamohamed S, Latourelle JC, Racette BA, Perlmutter JS, Wooten GF, Lew M, Klein C, Shill H, Golbe LI, Mark MH, Guttman M, Nicholson G, Wilk JB, Saint-Hilaire M, DeStefano AL, Prakash R, Tobin S, Williamson J, Suchowersky O, Labell N, Growdon BN, Singer C, Watts R, Goldwurm S, Pezzoli G, Baker KB, Giroux ML, Pramstaller PP, Burn DJ, Chinnery P, Sherman S, Vieregge P, Litvan I, Gusella JF, Myers RH and Parsian A. BDNF genetic variants are associated with onset age of familial Parkinson disease: GenePD Study. Neurology 2005; 65: 1823-1825.
274. Voineskos AN, Lerch JP, Felsky D, Shaikh S, Rajji TK, Miranda D, Lobaugh NJ, Mulsant BH, Pollock BG and Kennedy JL. The brain-derived neurotrophic factor Val66Met polymorphism and prediction of neural risk for Alzheimer disease. Arch Gen Psychiatry 2011; 68: 198-206.
275. Chen DY, Bambah-Mukku D, Pollonini G and Alberini CM. Glucocorticoid receptors recruit the CaMKII alpha-BDNF-CREB pathways to mediate memory consolidation. Nature Neuroscience 2012; 15: 1707-14.
276. Choi JM, Hong JH, Chae MJ, Ngyuen PH, Kang HS, Ma HI and Kim YJ. Analysis of mutations and the association between polymorphisms in the cerebral dopamine neurotrophic factor (CDNF) gene and Parkinson disease. Neurosci Lett 2011; 493: 97-101.
277. Lin LF, Doherty DH, Lile JD, Bektesh S and Collins F. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 1993; 260: 1130-1132.
278. Gash DM, Zhang Z, Ovadia A, Cass WA, Yi A, Simmerman L, Russell D, Martin D, Lapchak PA, Collins F, Hoffer BJ and Gerhardt GA. Functional recovery in parkinsonian monkeys treated with GDNF. Nature 1996; 380: 252-255.
279. Patani N, Jiang WG and Mokbel K. Brain-derived neurotrophic factor expression predicts adverse pathological & clinical outcomes in human breast cancer. Cancer Cell Int 2011; 11: 23.
280. Cao L and During MJ. What is the brain-cancer connection? Annu Rev Neurosci 2012; 35: 331-345.
281. Calado RT and Young NS. Telomere diseases. N Engl J Med 2009; 361: 2353-2365.
282. Hadley EC, Lakatta EG, Morrison-Bogorad M, Warner HR and Hodes RJ. The future of aging therapies. Cell 2005; 120: 557-567.
283. Honig LS, Kang MS, Schupf N, Lee JH and Mayeux R. Association of shorter leukocyte telomere repeat length with dementia and mortality. Arch Neurol 2012; 69: 1332-1339.
284. Rolyan H, Scheffold A, Heinrich A, Begus-Nahrmann Y, Langkopf BH, Holter SM, Vogt-Weisenhorn DM, Liss B, Wurst W, Lie DC, Thal DR, Biber K and Rudolph KL. Telomere shortening reduces Alzheimer's disease amyloid pathology in mice. Brain 2011; 134: 2044-2056.
285. Wang H, Chen H, Gao X, McGrath M, Deer D, De Vivo I, Schwarzschild MA and Ascherio A. Telomere length and risk of Parkinson's disease. Mov Disord 2008; 23: 302-305.
286. Eerola J, Kananen L, Manninen K, Hellstrom O, Tienari PJ and Hovatta I. No evidence for shorter leukocyte telomere length in Parkinson's disease patients. J Gerontol A Biol Sci Med Sci 2010; 65: 1181-1184.
287. Hudson G, Faini D, Stutt A, Eccles M, Robinson L, Burn DJ and Chinnery PF. No evidence of substantia nigra telomere shortening in Parkinson's disease. Neurobiol Aging 2011; 32: 2107, e2103-2105.
288. Njajou OT, Blackburn EH, Pawlikowska L, Mangino M, Damcott CM, Kwok PY, Spector TD, Newman AB, Harris TB, Cummings SR, Cawthon RM, Shuldiner AR, Valdes AM and Hsueh WC. A common variant in the telomerase RNA component is associated with short telomere length. PLoS One 2010; 5: e13048.
289. Shen Q, Zhang Z, Yu L, Cao L, Zhou D, Kan M, Li B, Zhang D, He L and Liu Y. Common variants near TERC are associated with leukocyte telomere length in the Chinese Han population. Eur J Hum Genet 2011; 19: 721-723.
290. Kim S, Parks CG, Xu Z, Carswell G, DeRoo LA, Sandler DP and Taylor JA. Association between genetic variants in DNA and histone methylation and telomere length. PLoS One 2012; 7: e40504.
291. Deelen J, Uh HW, Monajemi R, van Heemst D, Thijssen PE, Bohringer S, van den Akker EB, de Craen AJ, Rivadeneira F, Uitterlinden AG, Westendorp RG, Goeman JJ, Slagboom PE, Houwing-Duistermaat JJ and Beekman M. Gene set analysis of GWAS data for human longevity highlights the relevance of the insulin/IGF-1 signaling and telomere maintenance pathways. Age (Dordr) 2013; 35: 235-249.
292. Fossel M. Telomerase and the aging cell: implications for human health. JAMA 1998; 279: 1732-1735.
293. Bertram L, McQueen MB, Mullin K, Blacker D and Tanzi RE. Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat Genet 2007; 39: 17-23.
294. Lill CM, Roehr JT, McQueen MB, Kavvoura FK, Bagade S, Schjeide BM, Schjeide LM, Meissner E, Zauft U, Allen NC, Liu T, Schilling M, Anderson KJ, Beecham G, Berg D, Biernacka JM, Brice A, DeStefano AL, Do CB, Eriksson N, Factor SA, Farrer MJ, Foroud T, Gasser T, Hamza T, Hardy JA, Heutink P, Hill-Burns EM, Klein C, Latourelle JC, Maraganore DM, Martin ER, Martinez M, Myers RH, Nalls MA, Pankratz N, Payami H, Satake W, Scott WK, Sharma M, Singleton AB, Stefansson K, Toda T, Tung JY, Vance J, Wood NW, Zabetian CP; 23andMe Genetic Epidemiology of Parkinson's Disease Consortium; International Parkinson's Disease Genomics Consortium; Parkinson's Disease GWAS Consortium; Wellcome Trust Case Control Consortium 2); Young P, Tanzi RE, Khoury MJ, Zipp F, Lehrach H, Ioannidis JP, Bertram L. Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDGene database. PLoS Genet 2012; 8: e1002548.
295. Maloney B, Ge YW, Petersen RC, Hardy J, Rogers JT, Perez-Tur J and Lahiri DK. Functional characterization of three single-nucleotide polymorphisms present in the human APOE promoter sequence: Differential effects in neuronal cells and on DNA-protein interactions. Am J Med Genet B Neuropsychiatr Genet 2010; 153B: 185-201.
296. Citron BA, Dennis JS, Zeitlin RS and Echeverria V. Transcription factor Sp1 dysregulation in Alzheimer's disease. J Neurosci Res 2008; 86: 2499-2504.
297. Chu J, Zhuo JM and Pratico D. Transcriptional regulation of beta-secretase-1 by 12/15-lipoxygenase results in enhanced amyloidogenesis and cognitive impairments. Ann Neurol 2012; 71: 57-67.
298. Santpere G, Nieto M, Puig B and Ferrer I. Abnormal Sp1 transcription factor expression in Alzheimer disease and tauopathies. Neurosci Lett 2006; 397: 30-34.
299. Karin M, Liu Z and Zandi E. AP-1 function and regulation. Curr Opin Cell Biol 1997; 9: 240-246.
300. Calon F, Grondin R, Morissette M, Goulet M, Blanchet PJ, Di Paolo T and Bedard PJ. Molecular basis of levodopa-induced dyskinesias. Ann Neurol 2000; 47: S70-78.
301. Andersson M, Konradi C and Cenci MA. cAMP response element-binding protein is required for dopamine-dependent gene expression in the intact but not the dopamine-denervated striatum. J Neurosci 2001; 21: 9930-9943.
302. Jegga AG, Schneider L, Ouyang X and Zhang J. Systems biology of the autophagy-lysosomal pathway. Autophagy 2011; 7: 477-489.
303. Fahrig T, Gerlach I and Horvath E. A synthetic derivative of the natural product rocaglaol is a potent inhibitor of cytokine-mediated signaling and shows neuroprotective activity in vitro and in animal models of Parkinson's disease and traumatic brain injury. Mol Pharmacol 2005; 67: 1544-1555.
304. Perez-Cadahia B, Drobic B and Davie JR. Activation and function of immediate-early genes in the nervous system. Biochem Cell Biol 2011; 89: 61-73.
305. Gomez Ravetti M, Rosso OA, Berretta R and Moscato P. Uncovering molecular biomarkers that correlate cognitive decline with the changes of hippocampus' gene expression profiles in Alzheimer's disease. PLoS One 2010; 5: e10153.
306. Lu Y, Li T, Qureshi HY, Han D and Paudel HK. Early growth response 1 (Egr-1) regulates phosphorylation of microtubule-associated protein tau in mammalian brain. J Biol Chem 2011; 286: 20569-20581.
307. Lindersson EK, Hojrup P, Gai WP, Locker D, Martin D and Jensen PH. alpha-Synuclein filaments bind the transcriptional regulator HMGB-1. Neuroreport 2004; 15: 2735-2739.
308. Takata K, Kitamura Y, Kakimura J, Shibagaki K, Tsuchiya D, Taniguchi T, Smith MA, Perry G and Shimohama S. Role of high mobility group protein-1 (HMG1) in amyloid-beta homeostasis. Biochem Biophys Res Commun 2003; 301: 699-703.
309. Takata K, Takada T, Ito A, Asai M, Tawa M, Saito Y, Ashihara E, Tomimoto H, Kitamura Y and Shimohama S. Microglial Amyloid-beta1-40 Phagocytosis Dysfunction Is Caused by High-Mobility Group Box Protein-1: Implications for the Pathological Progression of Alzheimer's Disease. Int J Alzheimers Dis 2012; 2012: 685739.
310. Scaffidi P, Misteli T and Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 2002; 418: 191-195.
311. Gao HM, Zhou H, Zhang F, Wilson BC, Kam W and Hong JS. HMGB1 acts on microglia Mac1 to mediate chronic neuroinflammation that drives progressive neurodegeneration. J Neurosci 2011; 31: 1081-1092.
312. Clifford DB, Fagan AM, Holtzman DM, Morris JC, Teshome M, Shah AR and Kauwe JS. CSF biomarkers of Alzheimer disease in HIV-associated neurologic disease. Neurology 2009; 73: 1982-1987.
313. Giunta B, Hou H, Zhu Y, Rrapo E, Tian J, Takashi M, Commins D, Singer E, He J, Fernandez F and Tan J. HIV-1 Tat contributes to Alzheimer's disease-like pathology in PSAPP mice. Int J Clin Exp Pathol 2009; 2: 433-443.
314. Hickman SE, Allison EK and El Khoury J. Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer's disease mice. J Neurosci 2008; 28: 8354-8360.
315. Tarassishin L, Loudig O, Bauman A, Shafit-Zagardo B, Suh HS and Lee SC. Interferon regulatory factor 3 inhibits astrocyte inflammatory gene expression through suppression of the proinflammatory miR-155 and miR-155*. Glia 2011; 59: 1911-1922.
316. Chakrabarty P, Ceballos-Diaz C, Lin WL, Beccard A, Jansen-West K, McFarland NR, Janus C, Dickson D, Das P and Golde TE. Interferon-gamma induces progressive nigrostriatal degeneration and basal ganglia calcification. Nat Neurosci 2011; 14: 694-696.
317. Soares HD, Potter WZ, Pickering E, Kuhn M, Immermann FW, Shera DM, Ferm M, Dean RA, Simon AJ, Swenson F, Siuciak JA, Kaplow J, Thambisetty M, Zagouras P, Koroshetz WJ, Wan HI, Trojanowski JQ, Shaw LM; Biomarkers Consortium Alzheimer's Disease Plasma Proteomics Project. Plasma biomarkers associated with the apolipoprotein E genotype and Alzheimer disease. Arch Neurol 2012; 69: 1310-1317.
318. Barcia C, Ros CM, Annese V, Gomez A, Ros-Bernal F, Aguado-Yera D, Martinez-Pagan ME, de Pablos V, Fernandez-Villalba E and Herrero MT. IFN-gamma signaling, with the synergistic contribution of TNF-alpha, mediates cell specific microglial and astroglial activation in experimental models of Parkinson's disease. Cell Death Dis 2011; 2: e142.
319. Jaeger S and Pietrzik CU. Functional role of lipoprotein receptors in Alzheimer's disease. Curr Alzheimer Res 2008; 5: 15-25.
320. Waldron E, Heilig C, Schweitzer A, Nadella N, Jaeger S, Martin AM, Weggen S, Brix K and Pietrzik CU. LRP1 modulates APP trafficking along early compartments of the secretory pathway. Neurobiol Dis 2008; 31: 188-197.
321. Liu Q, Trotter J, Zhang J, Peters MM, Cheng H, Bao J, Han X, Weeber EJ and Bu G. Neuronal LRP1 knockout in adult mice leads to impaired brain lipid metabolism and progressive, age-dependent synapse loss and neurodegeneration. J Neurosci 2010; 30: 17068-17078.
322. Sloan CD, Shen L, West JD, Wishart HA, Flashman LA, Rabin LA, Santulli RB, Guerin SJ, Rhodes CH, Tsongalis GJ, McAllister TW, Ahles TA, Lee SL, Moore JH and Saykin AJ. Genetic pathway-based hierarchical clustering analysis of older adults with cognitive complaints and amnestic mild cognitive impairment using clinical and neuroimaging phenotypes. Am J Med Genet B Neuropsychiatr Genet 2010; 153B: 1060-1069.
323. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, McCarthy MI, Ramos EM, Cardon LR, Chakravarti A, Cho JH, Guttmacher AE, Kong A, Kruglyak L, Mardis E, Rotimi CN, Slatkin M, Valle D, Whittemore AS, Boehnke M, Clark AG, Eichler EE, Gibson G, Haines JL, Mackay TF, McCarroll SA and Visscher PM. Finding the missing heritability of complex diseases. Nature 2009; 461: 747-753.
324. Zuk O, Hechter E, Sunyaev SR and Lander ES. The mystery of missing heritability: Genetic interactions create phantom heritability. Proc Natl Acad Sci U S A 2012; 109: 1193-1198.
325. Peregrin-Alvarez JM, Sanford C and Parkinson J. The conservation and evolutionary modularity of metabolism. Genome Biol 2009; 10: R63.
326. Ayalew M, Le-Niculescu H, Levey DF, Jain N, Changala B, Patel SD, Winiger E, Breier A, Shekhar A, Amdur R, Koller D, Nurnberger JI, Corvin A, Geyer M, Tsuang MT, Salomon D, Schork NJ, Fanous AH, O'Donovan MC and Niculescu AB. Convergent functional genomics of schizophrenia: from comprehensive understanding to genetic risk prediction. Mol Psychiatry 2012; 17: 887-905.
327. Zhong H, Yang X, Kaplan LM, Molony C and Schadt EE. Integrating pathway analysis and genetics of gene expression for genome-wide association studies. Am J Hum Genet 2010; 86: 581-591.
328. Ala-Korpela M, Kangas AJ and Inouye M. Genome-wide association studies and systems biology: together at last. Trends Genet 2011; 27: 493-498.