The role of APP proteolytic processing in lipid metabolism

Experimental Brain Research

Volumn 217, Issue 3-4, 2012, Pages 365-375

  Grimm, Marcus O W ^a   Rothhaar, Tatjana L ^a   Hartmann, Tobias ^a  

^a SAARLAND UNIVERSITY   (Germany)

Author keywords

Abeta; Alzheimer's disease; APP processing; Cholesterol; Lipids; Neurodegeneration; Physiological function; Sphingolipids

Indexed keywords

ALPHA SECRETASE; AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; ANTERIOR PHARYNX DEFECTIVE 1 PROTEIN; APOLIPOPROTEIN E; BETA SECRETASE 1; CERAMIDE; CHOLESTEROL; CYTOSOLIC PHOSPHOLIPASE A2; GANGLIOSIDE; GANGLIOSIDE GM1; GANGLIOSIDE GM2; GLYCOGEN SYNTHASE KINASE 3BETA; NICASTRIN; PLASMALOGEN; PRESENILIN; PROTEIN AMYLOID PRECURSOR PROTEIN INTRACELLULAR DOMAIN 1; PROTEIN AMYLOID PRECURSOR PROTEIN INTRACELLULAR DOMAIN 2; PROTEIN FE65; REACTIVE OXYGEN METABOLITE; SPHINGOLIPID; SPHINGOMYELIN; SPHINGOMYELIN PHOSPHODIESTERASE; SPHINGOSINE KINASE; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; AMYLOID PLAQUE; CHOLESTEROL SYNTHESIS; GENE EXPRESSION; GENETIC TRANSCRIPTION; HOMEOSTASIS; HUMAN; LIPID COMPOSITION; LIPID METABOLISM; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; OXIDATIVE STRESS; PHOSPHOLIPID SYNTHESIS; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; REVIEW;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; HUMANS; LIPID METABOLISM; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEOLYSIS;

EID: 84862897184     PISSN: 00144819     EISSN: 14321106     Source Type: Journal    
DOI: 10.1007/s00221-011-2975-6     Document Type: Review

References (126)

1. Alessenko AV, Bugrova AE, Dudnik LB (2004) Connection of lipid peroxide oxidation with the sphingomyelin pathway in the development of Alzheimer's disease. Biochem Soc Trans 32:144-146 (Pubitemid 38283036)
2. Ando S, Tanaka Y, Waki H, Kon K, Iwamoto M, Fukui F (1998) Gangliosides and sialylcholesterol as modulators of synaptic functions. Ann N Y Acad Sci 845:232-239 (Pubitemid 28365314)
3. Ariga T, Kobayashi K, Hasegawa A, Kiso M, Ishida H, Miyatake T (2001) Characterization of high-affinity binding between gangliosides and amyloid beta-protein. Arch Biochem Biophys 388:225-230 (Pubitemid 32911613)
4. Ariga T, Wakade C, Yu RK (2011) The pathological roles of ganglioside metabolism in Alzheimer's disease: effects of gangliosides on neurogenesis. Int J Alzheimers Dis 2011:193618
5. Ariga T, Yanagisawa M, Wakade C, Ando S, Buccafusco JJ, McDonald MP, Yu RK (2010) Ganglioside metabolism in a transgenic mouse model of Alzheimer's disease: expression of Chol-1alpha antigens in the brain. ASN Neuro 2:233-241
6. Aydin D, Filippov MA, Tschape JA, Gretz N, Prinz M, Eils R, Brors B, Muller UC (2011) Comparative transcriptome profiling of amyloid precursor protein family members in the adult cortex. BMC Genom 12:160
7. Baek SH, Ohgi KA, Rose DW, Koo EH, Glass CK, Rosenfeld MG (2002) Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-kappaB and beta-amyloid precursor protein. Cell 110:55-67 (Pubitemid 34874606)
8. Balci-Hayta B, Erdem-Ozdamar S, Dincer P (2011) Overexpression of amyloid beta precursor protein enhances expression and secretion of ST6Gal1 in C2C12 myogenic cell line. Cell Biol Int 35:9-13
9. Bandaru VV, Troncoso J, Wheeler D, Pletnikova O, Wang J, Conant K, Haughey NJ (2009) ApoE4 disrupts sterol and sphingolipid metabolism in Alzheimer's but not normal brain. Neurobiol Aging 30:591-599
10. Beel AJ, Sakakura M, Barrett PJ, Sanders CR (2010) Direct binding of cholesterol to the amyloid precursor protein: an important interaction in lipid-Alzheimer's disease relationships? Biochim Biophys Acta 1801:975-982
11. Belyaev ND, Kellett KA, Beckett C, Makova NZ, Revett TJ, Nalivaeva NN, Hooper NM, Turner AJ (2010) The transcriptionally active amyloid precursor protein (APP) intracellular domain is preferentially produced from the 695 isoform of APP in a {beta}-secre-tase-dependent pathway. J Biol Chem 285:41443-41454
12. Bernardo A, Harrison FE, McCord M, Zhao J, Bruchey A, Davies SS, Jackson Roberts L, Mathews PM II, Matsuoka Y, Ariga T, Yu RK, Thompson R, McDonald MP (2009) Elimination of GD3 synthase improves memory and reduces amyloid-beta plaque load in transgenic mice. Neurobiol Aging 30:1777-1791
13. Bryleva EY, Rogers MA, Chang CC, Buen F, Harris BT, Rousselet E, Seidah NG, Oddo S, LaFerla FM, Spencer TA, Hickey WF, Chang TY (2010) ACAT1 gene ablation increases 24(S)-hydrox-ycholesterol content in the brain and ameliorates amyloid pathology in mice with AD. Proc Natl Acad Sci USA 107:3081-3086
14. Cao X, Sudhof TC (2001) A transcriptionally [correction of tran-scriptively] active complex of APP with Fe65 and histone acetyl-transferase Tip60. Science 293:115-120 (Pubitemid 32625507)
15. Checler F, Sunyach C, Pardossi-Piquard R, Sevalle J, Vincent B, Kawarai T, Girardot N, St George-Hyslop P, da Costa CA (2007) The gamma/epsilon- secretase-derived APP intracellular domain fragments regulate p53. Curr Alzheimer Res 4:423-426 (Pubitemid 47416636)
16. Chen TY, Liu PH, Ruan CT, Chiu L, Kung FL (2006) The intracellular domain of amyloid precursor protein interacts with flotillin-1, a lipid raft protein. Biochem Biophys Res Commun 342:266-272 (Pubitemid 43247386)
17. Cheng H, Xu J, McKeel DW Jr, Han X (2003) Specificity and potential mechanism of sulfatide deficiency in Alzheimer's disease: an electrospray ionization mass spectrometric study. Cell Mol Biol (Noisy-le-grand) 49:809-818
18. Choo-Smith LP, Garzon-Rodriguez W, Glabe CG, Surewicz WK (1997) Acceleration of amyloid fibril formation by specific binding of Abeta-(1-40) peptide to ganglioside-containing membrane vesicles. J Biol Chem 272:22987-22990 (Pubitemid 27392420)
19. Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 261:921-923 (Pubitemid 23275809)
20. Cordy JM, Hussain I, Dingwall C, Hooper NM, Turner AJ (2003) Exclusively targeting beta-secretase to lipid rafts by GPI-anchor addition up-regulates beta-site processing of the amyloid precursor protein. Proc Natl Acad Sci USA 100:11735-11740 (Pubitemid 37206004)
21. Cutler RG, Kelly J, Storie K, Pedersen WA, Tammara A, Hatanpaa K, Troncoso JC, Mattson MP (2004) Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease. Proc Natl Acad Sci USA 101:2070-2075 (Pubitemid 38229016)
22. Daigle I, Li C (1993) apl-1, a Caenorhabditis elegans gene encoding a protein related to the human beta-amyloid protein precursor. Proc Natl Acad Sci USA 90:12045-12049
23. Dawson GR, Seabrook GR, Zheng H, Smith DW, Graham S, O'Dowd G, Bowery BJ, Boyce S, Trumbauer ME, Chen HY, Van der Ploeg LH, Sirinathsinghji DJ (1999) Age-related cognitive deficits, impaired long-term potentiation and reduction in synaptic marker density in mice lacking the beta-amyloid precursor protein. Neuroscience 90:1-13 (Pubitemid 29096448)
24. De Strooper B (2003) Aph-1, Pen-2, and Nicastrin with Presenilin generate an active gamma-Secretase complex. Neuron 38:9-12 (Pubitemid 36423348)
25. de Vet EC, Ijlst L, Oostheim W, Wanders RJ, van den Bosch H (1998) Alkyl-dihydroxyacetonephosphate synthase. Fate in peroxisome biogenesis disorders and identification of the point mutation underlying a single enzyme deficiency. J Biol Chem 273:10296-10301 (Pubitemid 28227633)
26. Derrington EA, Borroni E (1990) The developmental expression of the cholinergic-specific antigen Chol-1 in the central and peripheral nervous system of the rat. Brain Res Dev Brain Res 52:131-140 (Pubitemid 20081070)
27. Duering M, Grimm MO, Grimm HS, Schroder J, Hartmann T (2005) Mean age of onset in familial Alzheimer's disease is determined by amyloid beta 42. Neurobiol Aging 26:785-788 (Pubitemid 40249479)
28. Engel T, Hernandez F, Avila J, Lucas JJ (2006) Full reversal of Alzheimer's disease-like phenotype in a mouse model with conditional overexpression of glycogen synthase kinase-3. J Neurosci 26:5083-5090 (Pubitemid 44315289)
29. Fassbender K, Simons M, Bergmann C, Stroick M, Lutjohann D, Keller P, Runz H, Kuhl S, Bertsch T, von Bergmann K, Hennerici M, Beyreuther K, Hartmann T (2001) Simvastatin strongly reduces levels of Alzheimer's disease beta -amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo. Proc Natl Acad Sci USA 98:5856-5861 (Pubitemid 32435732)
30. Feldman HH, Doody RS, Kivipelto M, Sparks DL, Waters DD, Jones RW, Schwam E, Schindler R, Hey-Hadavi J, DeMicco DA, Breazna A (2010) Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. Neurology 74:956-964
31. Ghosal K, Vogt DL, Liang M, Shen Y, Lamb BT, Pimplikar SW (2009) Alzheimer's disease-like pathological features in transgenic mice expressing the APP intracellular domain. Proc Natl Acad Sci USA 106:18367-18372
32. Ghosh M, Tucker DE, Burchett SA, Leslie CC (2006) Properties of the Group IV phospholipase A2 family. Prog Lipid Res 45:487-510
33. Giliberto L, d'Abramo C, Acker CM, Davies P, D'Adamio L (2010) Transgenic expression of the amyloid-beta precursor protein-intracellular domain does not induce Alzheimer's disease-like traits in vivo. PLoS One 5:e11609
34. Ginsberg L, Rafique S, Xuereb JH, Rapoport SI, Gershfeld NL (1995) Disease and anatomic specificity of ethanolamine plasmalogen deficiency in Alzheimer's disease brain. Brain Res 698:223-226
35. Gottfries CG (1996) Neurochemistry and neurotransmitters. Int Psychogeriatr 8(Suppl 3):225-231
36. Grimm MO, Grimm HS, Hartmann T (2007) Amyloid beta as a regulator of lipid homeostasis. Trends Mol Med 13:337-344 (Pubitemid 47126987)
37. Grimm MO, Grimm HS, Patzold AJ, Zinser EG, Halonen R, Duering M, Tschape JA, De Strooper B, Muller U, Shen J, Hartmann T (2005) Regulation of cholesterol and sphingomyelin metabolism by amyloid-beta and presenilin. Nat Cell Biol 7:1118-1123
38. Grimm MO, Grimm HS, Tomic I, Beyreuther K, Hartmann T, Bergmann C (2008) Independent inhibition of Alzheimer disease beta-and gamma-secretase cleavage by lowered cholesterol levels. J Biol Chem 283:11302-11311
39. Grimm MO, Grosgen S, Riemenschneider M, Tanila H, Grimm HS, Hartmann T (2011a) From brain to food: Analysis of phosphat-idylcholins, lyso-phosphatidylcholins and phosphatidylcholin-plasmalogens derivates in Alzheimer's disease human post mortem brains and mice model via mass spectrometry. J Chromatogr A 1218:7713-7722
40. Grimm MO, Grosgen S, Rothhaar TL, Burg VK, Hundsdorfer B, Haupenthal VJ, Friess P, Muller U, Fassbender K, Riemenschneider M, Grimm HS, Hartmann T (2011b) Intracellular APP domain regulates serine-Palmitoyl-CoA transferase expression and is affected in Alzheimer's disease. Int J Alzheimers Dis 2011:695413
41. Grimm MO, Kuchenbecker J, Grosgen S, Burg VK, Hundsdorfer B, Rothhaar TL, Friess P, de Wilde MC, Broersen LM, Penke B, Peter M, Vigh L, Grimm HS, Hartmann T (2011c) Docosahexaenoic acid reduces amyloid beta production via multiple pleiotropic mechanisms. J Biol Chem 286:14028-14039
42. Grimm MO, Kuchenbecker J, Rothhaar TL, Grosgen S, Hundsdorfer B, Burg VK, Friess P, Muller U, Grimm HS, Riemenschneider M, Hartmann T (2011d) Plasmalogen synthesis is regulated via alkyldihydroxyacetonephosphate-synthase by amyloid precursor protein processing and is affected in Alzheimer's disease. J Neurochem 116:916-925
43. Grimm MO, Rothhaar TL, Grösgen S, Burg VK, Hundsdörfer B, Haupenthal VJ, Friess P, Kins S, Grimm HS, Hartmann T (2011e) Trans fatty acids enhance amyloidogenic processing of the Alzheimer Amyloid Precursor Protein (APP). J Nut Biol. doi:10.1016/j.jnutbio.2011.1006.1015
44. Grimm MO, Tomic I, Hartmann T (2002) Potential external source of A beta in biological samples. Nat Cell Biol 4:E164-E165; author reply E165-E166
45. Grimm MO, Tschape JA, Grimm HS, Zinser EG, Hartmann T (2006) Altered membrane fluidity and lipid raft composition in presenilin-deficient cells. Acta Neurol Scand Suppl 185:27-32 (Pubitemid 44015222)
46. Grösgen S, Grimm MO, Friess P, Hartmann T (2010) Role of amyloid beta in lipid homeostasis. Biochim Biophys Acta 1801:966-974
47. Grziwa B, Grimm MO, Masters CL, Beyreuther K, Hartmann T, Lichtenthaler SF (2003) The transmembrane domain of the amyloid precursor protein in microsomal membranes is on both sides shorter than predicted. J Biol Chem 278:6803-6808 (Pubitemid 36800669)
48. Haass C, Hung AY, Schlossmacher MG, Teplow DB, Selkoe DJ (1993) beta-Amyloid peptide and a 3-kDa fragment are derived by distinct cellular mechanisms. J Biol Chem 268:3021-3024 (Pubitemid 23070917)
49. Haass C, Schlossmacher MG, Hung AY, Vigo-Pelfrey C, Mellon A, Ostaszewski BL, Lieberburg I, Koo EH, Schenk D, Teplow DB et al (1992) Amyloid beta-peptide is produced by cultured cells during normal metabolism. Nature 359:322-325
50. Han X, MH D, McKeel DW Jr, Kelley J, Morris JC (2002) Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer's disease: potential role in disease pathogenesis. J Neurochem 82:809-818
51. Han X, Holtzman DM, McKeel DW Jr (2001) Plasmalogen deficiency in early Alzheimer's disease subjects and in animal models: molecular characterization using electrospray ionization mass spectrometry. J Neurochem 77:1168-1180 (Pubitemid 32467071)
52. Hanada K (2003) Serine palmitoyltransferase, a key enzyme of sphingolipid metabolism. Biochim Biophys Acta 1632:16-30 (Pubitemid 36628112)
53. Hartmann T, Fassbender K, Grimm MOW (2007a) Alzheimer's disease prevention - The emerging role of lipids and diet. OCL - Oleagineux Corps Gras Lipides 14:182-185 (Pubitemid 47407659)
54. Hartmann T, Kuchenbecker J, Grimm MO (2007b) Alzheimer's disease: the lipid connection. J Neurochem 103(Suppl 1):159-170
55. Haughey NJ, Liu D, Nath A, Borchard AC, Mattson MP (2002a) Disruption of neurogenesis in the subventricular zone of adult mice, and in human cortical neuronal precursor cells in culture, by amyloid beta-peptide: implications for the pathogenesis of Alzheimer's disease. Neuromolecular Med 1:125-135 (Pubitemid 37012521)
56. Haughey NJ, Nath A, Chan SL, Borchard AC, Rao MS, Mattson MP (2002b) Disruption of neurogenesis by amyloid beta-peptide, and perturbed neural progenitor cell homeostasis, in models of Alzheimer's disease. J Neurochem 83:1509-1524 (Pubitemid 35477489)
57. Hayashi H, Kimura N, Yamaguchi H, Hasegawa K, Yokoseki T, Shibata M, Yamamoto N, Michikawa M, Yoshikawa Y, Terao K, Matsuzaki K, Lemere CA, Selkoe DJ, Naiki H, Yanagisawa K (2004) A seed for Alzheimer amyloid in the brain. J Neurosci 24:4894-4902 (Pubitemid 38668215)
58. He X, Huang Y, Li B, Gong CX, Schuchman EH (2010) Deregulation of sphingolipid metabolism in Alzheimer's disease. Neurobiol Aging 31:398-408
59. Hebert SS, Serneels L, Tolia A, Craessaerts K, Derks C, Filippov MA, Muller U, De Strooper B (2006) Regulated intramembrane prote- olysis of amyloid precursor protein and regulation of expression of putative target genes. EMBO Rep 7:739-745 (Pubitemid 43986273)
60. Henriques AG, Vieira SI, e Silva EF, e Silva OA (2009) Alphabeta hinders nuclear targeting of AICD and Fe65 in primary neuronal cultures. J Mol Neurosci 39:248-255
61. Herz J, Bock HH (2002) Lipoprotein receptors in the nervous system. Annu Rev Biochem 71:405-434 (Pubitemid 34800226)
62. Holtzman DM, Bales KR, Tenkova T, Fagan AM, Parsadanian M, Sartorius LJ, Mackey B, Olney J, McKeel D, Wozniak D, Paul SM (2000) Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease. Proc Natl Acad Sci USA 97:2892-2897 (Pubitemid 30159268)
63. Hung AY, Koo EH, Haass C, Selkoe DJ (1992) Increased expression of beta-amyloid precursor protein during neuronal differentiation is not accompanied by secretory cleavage. Proc Natl Acad Sci USA 89:9439-9443
64. Igbavboa U, Sun GY, Weisman GA, He Y, Wood WG (2009) Amyloid beta-protein stimulates trafficking of cholesterol and caveolin-1 from the plasma membrane to the Golgi complex in mouse primary astrocytes. Neuroscience 162:328-338
65. Jana A, Pahan K (2004) Fibrillar amyloid-beta peptides kill human primary neurons via NADPH oxidase-mediated activation of neutral sphingomyelinase. Implications for Alzheimer's disease. J Biol Chem 279:51451-51459 (Pubitemid 40017893)
66. Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA (2000) Statins and the risk of dementia. Lancet 356:1627-1631
67. Jin K, Peel AL, Mao XO, Xie L, Cottrell BA, Henshall DC, Greenberg DA (2004) Increased hippocampal neurogenesis in Alzheimer's disease. Proc Natl Acad Sci USA 101:343-347 (Pubitemid 38084252)
68. Kalanj S, Kracun I, Rosner H, Cosovic C (1991) Regional distribution of brain gangliosides in Alzheimer's disease. Neurol Croat 40:269-281
69. Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, Multhaup G, Beyreuther K, Muller-Hill B (1987) The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature 325:733-736 (Pubitemid 17054046)
70. Katsel P, Li C, Haroutunian V (2007) Gene expression alterations in the sphingolipid metabolism pathways during progression of dementia and Alzheimer's disease: a shift toward ceramide accumulation at the earliest recognizable stages of Alzheimer's disease? Neurochem Res 32:845-856 (Pubitemid 46481322)
71. Kitazume S, Tachida Y, Oka R, Kotani N, Ogawa K, Suzuki M, Dohmae N, Takio K, Saido TC, Hashimoto Y (2003) Characterization of alpha 2, 6-sialyltransferase cleavage by Alzheimer's beta-secretase (BACE1). J Biol Chem 278:14865-14871 (Pubitemid 36799814)
72. Kracun I, Kalanj S, Cosovic C, Talan-Hranilovic J (1990) Brain gangliosides in Alzheimer's disease. J Hirnforsch 31:789-793
73. Kracun I, Kalanj S, Talan-Hranilovic J, Cosovic C (1992) Cortical distribution of gangliosides in Alzheimer's disease. Neurochem Int 20:433-438
74. Kriem B, Sponne I, Fifre A, Malaplate-Armand C, Lozac'h-Pillot K, Koziel V, Yen-Potin FT, Bihain B, Oster T, Olivier JL, Pillot T (2005) Cytosolic phospholipase A2 mediates neuronal apoptosis induced by soluble oligomers of the amyloid-beta peptide. FASEB J 19:85-87 (Pubitemid 40069926)
75. LaDu MJ, Falduto MT, Manelli AM, Reardon CA, Getz GS, Frail DE (1994) Isoform-specific binding of apolipoprotein E to beta-amyloid. J Biol Chem 269:23403-23406
76. Lammich S, Kojro E, Postina R, Gilbert S, Pfeiffer R, Jasionowski M, Haass C, Fahrenholz F (1999) Constitutive and regulated alpha-secretase cleavage of Alzheimer's amyloid precursor protein by a dis-integrin metalloprotease. Proc Natl Acad Sci USA 96:3922-3927 (Pubitemid 29169012)
77. Liu Q, Zerbinatti CV, Zhang J, Hoe HS, Wang B, Cole SL, Herz J, Muglia L, Bu G (2007) Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1. Neuron 56:66-78 (Pubitemid 47484175)
78. Liu WW, Todd S, Coulson DT, Irvine GB, Passmore AP, McGuinness B, McConville M, Craig D, Johnston JA (2009) A novel reciprocal and biphasic relationship between membrane cholesterol and beta-secretase activity in SH-SY5Y cells and in human platelets. J Neurochem 108:341-349
79. Lopez-Toledano MA, Shelanski ML (2004) Neurogenic effect of beta-amyloid peptide in the development of neural stem cells. J Neurosci 24:5439-5444 (Pubitemid 38747685)
80. Lopez-Toledano MA, Shelanski ML (2007) Increased neurogenesis in young transgenic mice overexpressing human APP(Sw, Ind). J Alzheimers Dis 12:229-240 (Pubitemid 350179250)
81. Lovestone S, Reynolds CH, Latimer D, Davis DR, Anderton BH, Gallo JM, Hanger D, Mulot S, Marquardt B, Stabel S et al (1994) Alzheimer's disease-like phosphorylation of the microtubule-associated protein tau by glycogen synthase kinase-3 in transfected mammalian cells. Curr Biol 4:1077-1086 (Pubitemid 124001594)
82. Luo LQ, Martin-Morris LE, White K (1990) Identification, secretion, and neural expression of APPL, a Drosophila protein similar to human amyloid protein precursor. J Neurosci 10:3849-3861
83. Mahley RW (1988) Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 240:622-630
84. Malaplate-Armand C, Florent-Bechard S, Youssef I, Koziel V, Sponne I, Kriem B, Leininger-Muller B, Olivier JL, Oster T, Pillot T (2006) Soluble oligomers of amyloid-beta peptide induce neuronal apoptosis by activating a cPLA2-dependent sphingomyelinase-ceramide pathway. Neurobiol Dis 23:178-189 (Pubitemid 43922461)
85. Mazur-Kolecka B, Golabek A, Nowicki K, Flory M, Frackowiak J (2006) Amyloid-beta impairs development of neuronal progenitor cells by oxidative mechanisms. Neurobiol Aging 27:1181-1192 (Pubitemid 44067306)
86. Molander-Melin M, Blennow K, Bogdanovic N, Dellheden B, Mansson JE, Fredman P (2005) Structural membrane alterations in Alzheimer brains found to be associated with regional disease development; increased density of gangliosides GM1 and GM2 and loss of cholesterol in detergent-resistant membrane domains. J Neurochem 92:171-182 (Pubitemid 40193519)
87. Muller T, Concannon CG, Ward MW, Walsh CM, Tirniceriu AL, Tribl F, Kogel D, Prehn JH, Egensperger R (2007) Modulation of gene expression and cytoskeletal dynamics by the amyloid precursor protein intracellular domain (AICD). Mol Biol Cell 18:201-210 (Pubitemid 46066721)
88. Nakayama K, Ohkawara T, Hiratochi M, Koh CS, Nagase H (2008) The intracellular domain of amyloid precursor protein induces neuron-specific apoptosis. Neurosci Lett 444:127-131
89. Okada T, Wakabayashi M, Ikeda K, Matsuzaki K (2007) Formation of toxic fibrils of Alzheimer's amyloid beta-protein-(1-40) by mon-osialoganglioside GM1, a neuronal membrane component. J Mol Biol 371:481-489 (Pubitemid 47048280)
90. Osenkowski P, Ye W, Wang R, Wolfe MS, Selkoe DJ (2008) Direct and potent regulation of gamma-secretase by its lipid microenvi-ronment. J Biol Chem 283:22529-22540
91. Ozaki T, Li Y, Kikuchi H, Tomita T, Iwatsubo T, Nakagawara A (2006) The intracellular domain of the amyloid precursor protein (AICD) enhances the p53-mediated apoptosis. Biochem Biophys Res Commun 351:57-63 (Pubitemid 44635406)
92. Panchal M, Loeper J, Cossec JC, Perruchini C, Lazar A, Pompon D, Duyckaerts C (2010) Enrichment of cholesterol in microdissected Alzheimer's disease senile plaques as assessed by mass spectrom-etry. J Lipid Res 51:598-605
93. Pardossi-Piquard R, Petit A, Kawarai T, Sunyach C, Alves da Costa C, Vincent B, Ring S, D'Adamio L, Shen J, Muller U, St George Hyslop P, Checler F (2005) Presenilin-dependent transcriptional control of the Abeta-degrading enzyme neprilysin by intracellular domains of betaAPP and APLP. Neuron 46:541-554 (Pubitemid 40797380)
94. Pettegrew JW, Panchalingam K, Hamilton RL, McClure RJ (2001) Brain membrane phospholipid alterations in Alzheimer's disease. Neurochem Res 26:771-782 (Pubitemid 32845968)
95. Prasad MR, Lovell MA, Yatin M, Dhillon H, Markesbery WR (1998) Regional membrane phospholipid alterations in Alzheimer's disease. Neurochem Res 23:81-88 (Pubitemid 28145695)
96. Puglielli L, Ellis BC, Saunders AJ, Kovacs DM (2003) Ceramide stabilizes beta-site amyloid precursor protein-cleaving enzyme 1 and promotes amyloid beta-peptide biogenesis. J Biol Chem 278:19777-19783 (Pubitemid 36799164)
97. Raychaudhuri M, Mukhopadhyay D (2011) AICD overexpression in neuro 2A cells regulates expression of PTCH1 and TRPC5. Int J Alzheimers Dis 2011, article ID 239453
98. Sabo SL, Ikin AF, Buxbaum JD, Greengard P (2001) The Alzheimer amyloid precursor protein (APP) and FE65, an APP-binding protein, regulate cell movement. J Cell Biol 153:1403-1414 (Pubitemid 34286125)
99. Sabo SL, Ikin AF, Buxbaum JD, Greengard P (2003) The amyloid precursor protein and its regulatory protein, FE65, in growth cones and synapses in vitro and in vivo. J Neurosci 23:5407-5415 (Pubitemid 36807814)
100. Sanchez-Mejia RO, Newman JW, Toh S, Yu GQ, Zhou Y, Halabisky B, Cisse M, Scearce-Levie K, Cheng IH, Gan L, Palop JJ, Bonventre JV, Mucke L (2008) Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer's disease. Nat Neurosci 11:1311-1318
101. Satoi H, Tomimoto H, Ohtani R, Kitano T, Kondo T, Watanabe M, Oka N, Akiguchi I, Furuya S, Hirabayashi Y, Okazaki T (2005) Astroglial expression of ceramide in Alzheimer's disease brains: a role during neuronal apoptosis. Neuroscience 130:657-666 (Pubitemid 39601439)
102. Sawamura N, Morishima-Kawashima M, Waki H, Kobayashi K, Kuramochi T, Frosch MP, Ding K, Ito M, Kim TW, Tanzi RE, Oyama F, Tabira T, Ando S, Ihara Y (2000) Mutant presenilin 2 transgenic mice. A large increase in the levels of Abeta 42 is presumably associated with the low density membrane domain that contains decreased levels of glycerophospholipids and sphingomyelin. J Biol Chem 275:27901-27908
103. Simons M, Keller P, De Strooper B, Beyreuther K, Dotti CG, Simons K (1998) Cholesterol depletion inhibits the generation of betaamyloid in hippocampal neurons. Proc Natl Acad Sci USA 95:6460-6464 (Pubitemid 28249035)
104. Simons M, Schwarzler F, Lutjohann D, von Bergmann K, Beyreuther K, Dichgans J, Wormstall H, Hartmann T, Schulz JB (2002) Treatment with simvastatin in normocholesterolemic patients with Alzheimer's disease: a 26-week randomized, placebo-controlled, double-blind trial. Ann Neurol 52:346-350 (Pubitemid 35001502)
105. Sisodia SS, St George-Hyslop PH (2002) gamma-Secretase, Notch, Abeta and Alzheimer's disease: where do the presenilins fit in? Nat Rev Neurosci 3:281-290 (Pubitemid 135706607)
106. Slomnicki LP, Lesniak W (2008) A putative role of the amyloid precursor protein intracellular domain (AICD) in transcription. Acta Neurobiol Exp (Wars) 68:219-228 (Pubitemid 351871139)
107. Soba P, Eggert S, Wagner K, Zentgraf H, Siehl K, Kreger S, Lower A, Langer A, Merdes G, Paro R, Masters CL, Muller U, Kins S, Beyreuther K (2005) Homo- and heterodimerization of APP family members promotes intercellular adhesion. EMBO J 24:3624-3634 (Pubitemid 41509369)
108. Soderberg M, Edlund C, Alafuzoff I, Kristensson K, Dallner G (1992) Lipid composition in different regions of the brain in Alzheimer's disease/senile dementia of Alzheimer's type. J Neurochem 59:1646-1653
109. Sparks DL, Sabbagh MN, Connor DJ, Lopez J, Launer LJ, Browne P, Wasser D, Johnson-Traver S, Lochhead J, Ziolwolski C (2005) Atorvastatin for the treatment of mild to moderate Alzheimer disease: preliminary results. Arch Neurol 62:753-757 (Pubitemid 40656090)
110. Spiegel S, Kolesnick R (2002) Sphingosine 1-phosphate as a therapeutic agent. Leukemia 16:1596-1602
111. Steiner H, Fluhrer R, Haass C (2008) Intramembrane proteolysis by gamma-secretase. J Biol Chem 283:29627-29631
112. Svennerholm L, Gottfries CG (1994) Membrane lipids, selectively diminished in Alzheimer brains, suggest synapse loss as a primary event in early-onset form (type I) and demyelination in late-onset form (type II). J Neurochem 62:1039-1047 (Pubitemid 24064516)
113. Tamboli IY, Prager K, Barth E, Heneka M, Sandhoff K, Walter J (2005) Inhibition of glycosphingolipid biosynthesis reduces secretion of the beta-amyloid precursor protein and amyloid beta-peptide. J Biol Chem 280:28110-28117 (Pubitemid 41076929)
114. von Koch CS, Zheng H, Chen H, Trumbauer M, Thinakaran G, van der Ploeg LH, Price DL, Sisodia SS (1997) Generation of APLP2 KO mice and early postnatal lethality in APLP2/APP double KO mice. Neurobiol Aging 18:661-669 (Pubitemid 28046419)
115. von Rotz RC, Kohli BM, Bosset J, Meier M, Suzuki T, Nitsch RM, Konietzko U (2004) The APP intracellular domain forms nuclear multiprotein complexes and regulates the transcription of its own precursor. J Cell Sci 117:4435-4448 (Pubitemid 39360070)
116. Wang P, Yang G, Mosier DR, Chang P, Zaidi T, Gong YD, Zhao NM, Dominguez B, Lee KF, Gan WB, Zheng H (2005) Defective neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-Like protein 2. J Neurosci 25:1219-1225 (Pubitemid 40268964)
117. Wasco W, Bupp K, Magendantz M, Gusella JF, Tanzi RE, Solomon F (1992) Identification of a mouse brain cDNA that encodes a protein related to the Alzheimer disease-associated amyloid beta protein precursor. Proc Natl Acad Sci USA 89:10758-10762
118. Wasco W, Gurubhagavatula S, Paradis MD, Romano DM, Sisodia SS, Hyman BT, Neve RL, Tanzi RE (1993) Isolation and characterization of APLP2 encoding a homologue of the Alzheimer's associated amyloid beta protein precursor. Nat Genet 5:95-100 (Pubitemid 23261528)
119. Wolozin B, Kellman W, Ruosseau P, Celesia GG, Siegel G (2000) Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol 57:1439-1443
120. Wolozin B, Wang SW, Li NC, Lee A, Lee TA, Kazis LE (2007) Simvastatin is associated with a reduced incidence of dementia and Parkinson's disease. BMC Med 5:20
121. Yang G, Gong YD, Gong K, Jiang WL, Kwon E, Wang P, Zheng H, Zhang XF, Gan WB, Zhao NM (2005) Reduced synaptic vesicle density and active zone size in mice lacking amyloid precursor protein (APP) and APP-like protein 2. Neurosci Lett 384:66-71 (Pubitemid 40826619)
122. Yu Y, He J, Zhang Y, Luo H, Zhu S, Yang Y, Zhao T, Wu J, Huang Y, Kong J, Tan Q, Li XM (2009) Increased hippocampal neurogenesis in the progressive stage of Alzheimer's disease phenotype in an APP/PS1 double transgenic mouse model. Hippocampus 19:1247-1253
123. Zha Q, Ruan Y, Hartmann T, Beyreuther K, Zhang D (2004) GM1 ganglioside regulates the proteolysis of amyloid precursor protein. Mol Psychiatry 9:946-952 (Pubitemid 39381958)
124. Zhang YW, Wang R, Liu Q, Zhang H, Liao FF, Xu H (2007) Presenilin/gamma-secretase-dependent processing of beta-amyloid precursor protein regulates EGF receptor expression. Proc Natl Acad Sci USA 104:10613-10618 (Pubitemid 47185713)
125. Zheng H, Jiang M, Trumbauer ME, Sirinathsinghji DJ, Hopkins R, Smith DW, Heavens RP, Dawson GR, Boyce S, Conner MW, Stevens KA, Slunt HH, Sisoda SS, Chen HY, Van der Ploeg LH (1995) beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. Cell 81:525-531
126. Zinser EG, Hartmann T, Grimm MO (2007) Amyloid beta-protein and lipid metabolism. Biochim Biophys Acta 1768:1991-2001 (Pubitemid 47161020)