Animal models for Alzheimer's disease and frontotemporal dementia: A perspective

ASN Neuro

Volumn 1, Issue 4, 2009, Pages 251-264

  Götz, Jürgen ^a   Götz, Naeman N ^a  

^a UNIVERSITY OF SYDNEY   (Australia)

Author keywords

Alzheimer's disease; Amyloid; Caenorhabditis elegans; Drosophila; Frontotemporal dementia; Mouse; Rat; TAR DNA binding protein 43 (TDP 43); Tau; Transgenic; Zebrafish

Indexed keywords

ALZHEIMER DISEASE VACCINE; AMYLOID BETA PROTEIN; CHOLINESTERASE INHIBITOR; MEMANTINE; PROTEASOME; TAU PROTEIN; THIOFLAVINE;

ALZHEIMER DISEASE; DIAGNOSTIC IMAGING; DNA IMMUNIZATION; EARLY DIAGNOSIS; EXPERIMENTAL MODEL; FRONTOTEMPORAL DEMENTIA; INFLAMMATION; INVERTEBRATE; MITOSIS; NONHUMAN; OXIDATIVE STRESS; PATHOGENESIS; REVIEW; TRANSGENIC ANIMAL; VERTEBRATE;

EID: 77951083963     PISSN: None     EISSN: 17590914     Source Type: Journal    
DOI: 10.1042/AN20090042     Document Type: Review

References (134)

1. Allen B, Ingram E, Takao M, Smith MJ, Jakes R, Virdee K, Yoshida H, Holzer M, Craxton M, Emson PC, Atzori C, Migheli A, Crowther RA, Ghetti B, Spillantini MG, Goedert M (2002) Abundant tau filaments and nonapoptotic neurodegeneration in transgenic mice expressing human P301S tau protein. J Neurosci 22:9340-9351.
2. Andorfer C, Kress Y, Espinoza M, de Silva R, Tucker KL, Barde YA, Duff K, Davies P (2003) Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms. J Neurochem 86:582-590.
3. Arnold SE, Hyman BT, Flory J, Damasio AR, Van Hoesen GW (1991) The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer's disease. Cereb Cortex 1:103-116.
4. Asuni AA, Boutajangout A, Quartermain D, Sigurdsson EM (2007) Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements. J Neurosci 27:9115-9129.
5. Bach P, Tschape JA, Kopietz F, Braun G, Baade JK, Wiederhold KH, Staufenbiel M, Prinz M, Deller T, Kalinke U, Buchholz CJ, Muller UC (2009) Vaccination with Aβ-displaying virus-like particles reduces soluble and insoluble cerebral Aβ and lowers plaque burden in APP transgenic mice. J Immunol 182:7613-7624.
6. Bacskai BJ, Hickey GA, Skoch J, Kajdasz ST, Wang Y, Huang GF, Mathis CA, Klunk WE, Hyman BT (2003) Four-dimensional multiphoton imaging of brain entry, amyloid binding, and clearance of an amyloid-β ligand in transgenic mice. Proc Natl Acad Sci USA 100:12462-12467.
7. Ballatore C, Lee VM, Trojanowski JQ (2007) Tau-mediated neurodegeneration in Alzheimer's disease and related disorders. Nat Rev Neurosci 8:663-672.
8. Bard F, Cannon C, Barbour R, Burke RL, Games D, Grajeda H, Guido T, Hu K, Huang J, Johnson-Wood K, Khan K, Kholodenko D, Lee M, Lieberburg I, Motter R, Nguyen M, Soriano F, Vasquez N, Weiss K, Welch B, Seubert P, Schenk D, Yednock T (2000) Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat Med 6:916-919.
9. Bertram L, Tanzi RE (2008) Thirty years of Alzheimer's disease genetics: the implications of systematic meta-analyses. Nat Rev Neurosci 9:768-778.
10. Billings LM, Oddo S, Green KN, McGaugh JL, Laferla FM (2005) Intraneuronal Aβ causes the onset of early Alzheimer's disease-related cognitive deficits in transgenic mice. Neuron 45:675-688.
11. Bolmont T, Clavaguera F, Meyer-Luehmann M, Herzig MC, Radde R, Staufenbiel M, Lewis J, Hutton M, Tolnay M, Jucker M (2007) Induction of tau pathology by intracerebral infusion of amyloid-β-containing brain extract and by amyloid-β deposition in APP x Tau transgenic mice. Am J Pathol 171:2012-2020.
12. Braak H, Braak E (1991) Neuropathological staging of Alzheimer-related changes. Acta Neuropathol (Berl) 82:239-259.
13. Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 24:197-211.
14. Brandt R, Gergou A, Wacker I, Fath T, Hutter H (2009) A Caenorhabditis elegans model of tau hyperphosphorylation: induction of developmental defects by transgenic overexpression of Alzheimer's disease-like modified tau. Neurobiol Aging 30:22-33.
15. Chen F, David D, Ferrari A, Götz J (2004a) Posttranslational modifications of tau: role in human tauopathies and modeling in transgenic animals. Curr Drug Targets 5:503-515.
16. Chen F, Wollmer MA, Hoerndli F, Münch G, Kuhla B, Rogaev EI, Tsolaki M, Papassotiropoulos A, Götz J (2004b) Role for glyoxalase I in Alzheimer's disease. Proc Natl Acad Sci USA 101:7687-7692.
17. Clavaguera F, Bolmont T, Crowther RA, Abramowski D, Frank S, Probst A, Fraser G, Stalder AK, Beibel M, Staufenbiel M, Jucker M, Goedert M, Tolnay M (2009) Transmission and spreading of tauopathy in transgenic mouse brain. Nat Cell Biol 11:909-913.
18. Cruts M, Van Broeckhoven C (2008) Loss of progranulin function in frontotemporal lobar degeneration. Trends Genet 24:186-194.
19. Cullen KM, Halliday GM (1998) Neurofibrillary degeneration and cell loss in the nucleus basalis in comparison to cortical Alzheimer pathology. Neurobiol Aging 19:297-306.
20. David D, Hoerndli F, Götz J (2005a) Functional genomics meets neurodegenerative disorders Part I: transcriptomic and proteomic technology. Prog Neurobiol 76:153-168.
21. David DC, Hauptmann S, Scherping I, Schuessel K, Keil U, Rizzu P, Ravid R, Dröse S, Brandt U, Müller WE, Eckert E, Götz J (2005b) Proteomic and functional analysis reveal a mitochondrial dysfunction in P301L tau transgenic mice. J Biol Chem 280:23802-23814.
22. David DC, Ittner LM, Gehrig P, Nergenau D, Shepherd C, Halliday G, Götz J (2006) β-Amyloid treatment of two complementary P301L tau-expressing Alzheimer's disease models reveals similar deregulated cellular processes. Proteomics 6:6566-6577.
23. Dawson HN, Cantillana V, Chen L, Vitek MP (2007) The tau N279K exon 10 splicing mutation recapitulates frontotemporal dementia and parkinsonism linked to chromosome 17 tauopathy in a mouse model. J Neurosci 27:9155-9168.
24. Desplats P, Lee HJ, Bae EJ, Patrick C, Rockenstein E, Crews L, Spencer B, Masliah E, Lee SJ (2009) Inclusion formation and neuronal cell death through neuron-to-neuron transmission of α-synuclein. Proc Natl Acad Sci USA 106:13010-13015.
25. Deters N, Ittner LM, Götz J (2008) Divergent phosphorylation pattern of tau in P301L tau transgenic mice. Eur J Neurosci. 28:137-147.
26. Deters N, Ittner LM, Götz J (2009) Substrate-specific reduction of PP2A activity exaggerates tau pathology. Biochem Biophys Res Commun 379:400-405.
27. Dickey C, Kraft C, Jinwal U, Koren J, Johnson A, Anderson L, Lebson L, Lee D, Dickson D, de Silva R, Binder LI, Morgan D, Lewis J (2009) Aging analysis reveals slowed tau turnover and enhanced stress response in a mouse model of tauopathy. Am J Pathol 174:228-238.
28. Dixit R, Ross JL, Goldman YE, Holzbaur EL (2008) Differential regulation of dynein and kinesin motor proteins by tau. Science 319:1086-1089.
29. Drake J, Link CD, Butterfield DA (2003) Oxidative stress precedes fibrillar deposition of Alzheimer's disease amyloid β-peptide (1-42) in a transgenic Caenorhabditis elegans model. Neurobiol Aging 24:415-420.
30. Eckert A, Hauptmann S, Scherping I, Meinhardt J, Rhein V, Drose S, Brandt U, Fandrich M, Muller WE, Götz J (2008) Oligomeric and fibrillar species of β-amyloid (Aβ42) both impair mitochondrial function in P301L tau transgenic mice. J Mol Med 86:1255-1267.
31. Ferrari A, Hoerndli F, Baechi T, Nitsch RM, Götz J (2003) β-Amyloid induces PHF-like tau filaments in tissue culture. J Biol Chem 278:40162-40168.
32. Forman MS, Lal D, Zhang B, Dabir DV, Swanson E, Lee VM, Trojanowski JQ. (2005) Transgenic mouse model of tau pathology in astrocytes leading to nervous system degeneration. J Neurosci 25:3539-3550.
33. Frost B, Jacks RL, Diamond MI (2009) Propagation of tau misfolding from the outside to the inside of a cell. J Biol Chem 284:12845-12852.
34. Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C, Carr T, Clemens J, Donaldson T, Gillespie F et al (1995) Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein. Nature 373:523-527.
35. Giannakopoulos P, Herrmann FR, Bussiere T, Bouras C, Kovari E, Perl DP, Morrison JH, Gold G, Hof PR (2003) Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease. Neurology 60:1495-1500.
36. Glabe CG (2008) Structural classification of toxic amyloid oligomers. J Biol Chem 283:29639-29643.
37. Goedert M, Baur CP, Ahringer J, Jakes R, Hasegawa M, Spillantini MG, Smith MJ, Hill F (1996) PTL-1, a microtubule-associated protein with tau-like repeats from the nematode Caenorhabditis elegans. J Cell Sci 109:2661-2672.
38. Golde TE, Petrucelli L, Lewis J (2009) Targeting Aβ and tau in Alzheimer's disease, an early interim report. Exp Neurol, doi:10.1016/j. expneurol.2009.07.035
39. Gomez-Isla T, Hollister R, West H, Mui S, Growdon JH, Petersen RC, Parisi JE, Hyman BT (1997) Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease. Ann Neurol 41:17-24.
40. Götz J (2001) Tau and transgenic animal models. Brain Res Brain Res Rev 35:266-286.
41. Götz J, Nitsch RM (2001) Compartmentalized tau hyperphosphorylation and increased levels of kinases in transgenic mice. Neuroreport 12:2007-2016.
42. Götz J, Chen F, Barmettler R, Nitsch RM (2001a) Tau filament formation in transgenic mice expressing P301L Tau. J Biol Chem 276:529-534.
43. Götz J, Chen F, van Dorpe J, Nitsch RM (2001b) Formation of neurofibrillary tangles in P301L tau transgenic mice induced by Aβ42 fibrils. Science 293:1491-1495.
44. Götz J, Ittner LM, Kins S (2006) Do axonal defects in tau and amyloid precursor protein transgenic animals model axonopathy in Alzheimer's disease? J Neurochem 98:993-1006.
45. Götz J, Deters N, Doldissen A, Bokhari L, Ke Y, Wiesner A, Schonrock N, Ittner LM (2007) A decade of tau transgenic animal models and beyond. Brain Pathol 17:91-103.
46. Götz J, Ittner LM (2008) Animal models of Alzheimer's disease and frontotemporal dementia. Nat Rev Neurosci 9:532-544.
47. Götz J, Ittner LM, Fandrich M, Schonrock N (2008a) Is tau aggregation toxic or protective: a sensible question in the absence of sensitive methods? J Alzheimers Dis 14:423-429.
48. Götz J, Ittner LM, Schonrock N, Cappai R (2008b) An update on the toxicity of Aβ in Alzheimer's disease. Neuropsychiatr Dis Treat 4:1033-1042.
49. Götz J, Schonrock N, Vissel B, Ittner LM (2009) Alzheimer's disease selective vulnerability and modelling in transgenic mice. J Alzheimers Dis 18:243-251.
50. Guillozet-Bongaarts AL, Cahill ME, Cryns VL, Reynolds MR, Berry RW, Binder LI (2006) Pseudophosphorylation of tau at serine 422 inhibits caspase cleavage: in vitro evidence and implications for tangle formation in vivo. J Neurochem 97:1005-1014.
51. Habicht G, Haupt C, Friedrich RP, Hortschansky P, Sachse C, Meinhardt J, Wieligmann K, Gellermann GP, Brodhun M, Götz J, Halbhuber KJ, Rocken C, Horn U, Fandrich M (2007) Directed selection of a conformational antibody domain that prevents mature amyloid fibril formation by stabilizing Aβ protofibrils. Proc Natl Acad Sci USA 104:19232-19237.
52. Hall GF, Cohen MJ (1983) Extensive dendritic sprouting induced by close axotomy of central neurons in the lamprey. Science 222:518-521.
53. Hall GF, Lee VM, Lee G, Yao J (2001) Staging of neurofibrillary degeneration caused by human tau overexpression in a unique cellular model of human tauopathy. Am J Pathol 158:235-246.
54. Hardy J (2006) Alzheimer's disease: the amyloid cascade hypothesis: an update and reappraisal. J Alzheimers Dis 9:151-153.
55. 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 JS, 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, Williams J (2009) Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nat Genet 41:1088-1093.
56. Higuchi M, Zhang B, Forman MS, Yoshiyama Y, Trojanowski JQ, Lee VM (2005) Axonal degeneration induced by targeted expression of mutant human tau in oligodendrocytes of transgenic mice that model glial tauopathies. J Neurosci 25:9434-9443.
57. Hoerndli FJ, Toigo M, Schild A, Götz J, Day PJ (2004) Reference genes identified in SH-SY5Y cells using custom-made gene arrays with validation by quantitative polymerase chain reaction. Anal Biochem 335:30-41.
58. Hoerndli F, David D, Götz J (2005) Functional genomics meets neurodegenerative disorders. Part II: application and data integration. Prog Neurobiol 76:169-188.
59. Hoerndli FJ, Pelech S, Papassotiropoulos A, Götz J (2007) Aβ treatment and P301L tau expression in an Alzheimer's disease tissue culture model act synergistically to promote aberrant cell cycle re-entry. Eur J Neurosci. 26:60-72.
60. Hornsten A, Lieberthal J, Fadia S, Malins R, Ha L, Xu X, Daigle I, Markowitz M, O'Connor G, Plasterk R, Li C (2007) APL-1, a Caenorhabditis elegans protein related to the human β-amyloid precursor protein, is essential for viability. Proc Natl Acad Sci USA 104:1971-1976.
61. Horowitz PM, Patterson KR, Guillozet-Bongaarts AL, Reynolds MR, Carroll CA, Weintraub ST, Bennett DA, Cryns VL, Berry RW, Binder LI (2004) Early N-terminal changes and caspase-6 cleavage of tau in Alzheimer's disease. J Neurosci 24:7895-7902.
62. Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G (1996) Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice. Science 274:99-102.
63. Iqbal K, Grundke-Iqbal I (2008) Alzheimer neurofibrillary degeneration: significance, etiopathogenesis, therapeutics and prevention. J Cell Mol Med 12:38-55.
64. Ittner LM, Götz J (2007) Pronuclear injection for the generation of transgenic mice. Nat Protoc 2:1206-1215.
65. Ittner LM, Fath T, Ke YD, Bi M, van Eersel J, Li KM, Gunning P, Götz J (2008) Parkinsonism and impaired axonal transport in a mouse model of frontotemporal dementia. Proc Natl Acad Sci USA 105:15997-16002.
66. Ittner LM, Ke YD, Götz J (2009) Phosphorylated tau interacts with c-Jun N-terminal kinase-interacting protein 1 (JIP1) in Alzheimer's disease. J Biol Chem 284:20909-20916.
67. Kaletta T, Hengartner MO (2006) Finding function in novel targets: C. elegans as a model organism. Nat Rev Drug Discov 5:387-398.
68. Kim D, Nguyen MD, Dobbin MM, Fischer A, Sananbenesi F, Rodgers JT, Delalle I, Baur JA, Sui G, Armour SM, Puigserver P, Sinclair DA, Tsai LH (2007) SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis. EMBO J 26:3169-3179.
69. Kim WH, Lee S, Jung C, Ahmed A, Lee G, Hall GF (2009) Interneuronal transfer of human tau between lamprey central neurons in situ. J Alzheimers Dis, in press.
70. Kins S, Crameri A, Evans DR, Hemmings BA, Nitsch RM, Götz J (2001) Reduced PP2A activity induces hyperphosphorylation and altered compartmentalization of tau in transgenic mice. J Biol Chem 276:38193-38200.
71. Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, Bergstrom M, Savitcheva I, Huang GF, Estrada S, Ausen B, Debnath ML, Barletta J, Price JC, Sandell J, Lopresti BJ, Wall A, Koivisto P, Antoni G, Mathis CA, Langstrom B (2004) Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann Neurol 55:306-319.
72. Koson P, Zilka N, Kovac A, Kovacech B, Korenova M, Filipcik P, Novak M (2008) Truncated tau expression levels determine life span of a rat model of tauopathy without causing neuronal loss or correlating with terminal neurofibrillary tangle load. Eur J Neurosci 28:239-246.
73. Kraemer BC, Zhang B, Leverenz JB, Thomas JH, Trojanowski JQ, Schellenberg GD (2003) From the Cover: neurodegeneration and defective neurotransmission in a Caenorhabditis elegans model of tauopathy. Proc Natl Acad Sci USA 100:9980-9985.
74. Kragh PM, Nielsen AL, Li J, Du Y, Lin L, Schmidt M, Bogh IB, Holm IE, Jakobsen JE, Johansen MG, Purup S, Bolund L, Vajta G, Jorgensen AL (2009) Hemizygous minipigs produced by random gene insertion and handmade cloning express the Alzheimer's disease-causing dominant mutation APPsw. Transgenic Res 18:545-558.
75. Kril JJ, Patel S, Harding AJ, Halliday GM (2002) Neuron loss from the hippocampus of Alzheimer's disease exceeds extracellular neurofibrillary tangle formation. Acta Neuropathol (Berl) 103:370-376.
76. Kurosinski P, Götz J (2002) Glial cells under physiologic and pathological conditions. Arch Neurol 59:1524-1528.
77. 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, Amouyel P (2009) Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Nat Genet 41:1094-1099.
78. Lazarov O, Robinson J, Tang YP, Hairston IS, Korade-Mirnics Z, Lee VM, Hersh LB, Sapolsky RM, Mirnics K, Sisodia SS (2005) Environmental enrichment reduces Aβ levels and amyloid deposition in transgenic mice. Cell 120:701-713.
79. Le Corre S, Klafki HW, Plesnila N, Hubinger G, Obermeier A, Sahagun H, Monse B, Seneci P, Lewis J, Eriksen J, Zehr C, Yue M, McGowan E, Dickson DW, Hutton M, Roder HM (2006) An inhibitor of tau hyperphosphorylation prevents severe motor impairments in tau transgenic mice. Proc Natl Acad Sci USA 103:9673-9678.
80. Lesne S, Koh MT, Kotilinek L, Kayed R, Glabe CG, Yang A, Gallagher M, Ashe KH (2006) A specific amyloid-β protein assembly in the brain impairs memory. Nature 440:352-357.
81. Levitan D, Greenwald I (1995) Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer's disease gene. Nature 377:351-354.
82. Lewis J, McGowan E, Rockwood J, Melrose H, Nacharaju P, Van Slegtenhorst M, Gwinn-Hardy K, Murphy PM, Baker M, Yu X, Duff K, Hardy J, Corral A, Lin WL, Yen SH, Dickson DW, Davies P, Hutton M (2000) Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Nat Genet 25:402-405.
83. Lewis J, Dickson DW, Lin W-L, Chisholm L, Corral A, Jones G, Yen S-H, Sahara N, Skipper L, Yager D, Eckman C, Hardy J, Hutton M, McGowan E (2001) Enhanced neurofibrillary degeneration in transgenic mice expressing mutant Tau and APP. Science 293:1487-1491.
84. Li X, Greenwald I (1997) HOP-1, a Caenorhabditis elegans presenilin, appears to be functionally redundant with SEL-12 presenilin and to facilitate LIN-12 and GLP-1 signaling. Proc Natl Acad Sci USA 94:12204-12209.
85. Lim GP, Calon F, Morihara T, Yang F, Teter B, Ubeda O, Salem N, Jr., Frautschy SA, Cole GM (2005) A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J Neurosci 25:3032-3040.
86. Link CD (1995) Expression of human β-amyloid peptide in transgenic Caenorhabditis elegans. Proc Natl Acad Sci USA 92:9368-9372.
87. Magnani E, Fan J, Gasparini L, Golding M, Williams M, Schiavo G, Goedert M, Amos LA, Spillantini MG (2007) Interaction of tau protein with the dynactin complex. EMBO J 26:4546-4554.
88. McDermott JB, Aamodt S, Aamodt E (1996) ptl-1, a Caenorhabditis elegans gene whose products are homologous to the tau microtubule-associated proteins. Biochemistry 35:9415-9423.
89. Meyer-Luehmann M, Spires-Jones TL, Prada C, Garcia-Alloza M, de Calignon A, Rozkalne A, Koenigsknecht-Talboo J, Holtzman DM, Bacskai BJ, Hyman BT (2008) Rapid appearance and local toxicity of amyloid-β plaques in a mouse model of Alzheimer's disease. Nature 451:720-724.
90. Minkeviciene R, Rheims S, Dobszay MB, Zilberter M, Hartikainen J, Fulop L, Penke B, Zilberter Y, Harkany T, Pitkanen A, Tanila H (2009) Amyloid β-induced neuronal hyperexcitability triggers progressive epilepsy. J Neurosci 29:3453-3462.
91. Miyasaka T, Ding Z, Gengyo-Ando K, Oue M, Yamaguchi H, Mitani S, Ihara Y (2005) Progressive neurodegeneration in C. elegans model of tauopathy. Neurobiol Dis 20:372-383.
92. Mocanu MM, Nissen A, Eckermann K, Khlistunova I, Biernat J, Drexler D, Petrova O, Schonig K, Bujard H, Mandelkow E, Zhou L, Rune G, Mandelkow EM (2008) The potential for β-structure in the repeat domain of tau protein determines aggregation, synaptic decay, neuronal loss, and coassembly with endogenous Tau in inducible mouse models of tauopathy. J Neurosci 28:737-748.
93. Morcos M, Hutter H (2009) The model Caenorhabditis elegans in diabetes mellitus and Alzheimer's disease. J Alzheimers Dis 16:897-908.
94. Mucke L, Masliah E, Yu GQ, Mallory M, Rockenstein EM, Tatsuno G, Hu K, Kholodenko D, Johnson-Wood K, McConlogue L (2000) High-level neuronal expression of aβ 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci 20:4050-4058.
95. Neumann M, Schulz-Schaeffer W, Crowther RA, Smith MJ, Spillantini MG, Goedert M, Kretzschmar HA (2001) Pick's disease associated with the novel Tau gene mutation K369I. Ann Neurol 50:503-513.
96. Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM, McCluskey LF, Miller BL, Masliah E, Mackenzie IR, Feldman H, Feiden W, Kretzschmar HA, Trojanowski JQ, Lee VM (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314:130-133.
97. Nikolaev A, McLaughlin T, O'Leary DD, Tessier-Lavigne M (2009) APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature 457:981-989.
98. Noorbakhsh F, Overall CM, Power C (2009) Deciphering complex mechanisms in neurodegenerative diseases: the advent of systems biology. Trends Neurosci 32:88-100.
99. Obregon DF, Rezai-Zadeh K, Bai Y, Sun N, Hou H, Ehrhart J, Zeng J, Mori T, Arendash GW, Shytle D, Town T, Tan J (2006) ADAM10 activation is required for green tea (-)-epigallocatechin-3-gallate-induced α-secretase cleavage of amyloid precursor protein. J Biol Chem 281:16419-16427.
100. Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, Metherate R, Mattson MP, Akbari Y, LaFerla FM (2003) Triple-transgenic model of Alzheimer's disease with plaques and tangles. Intracellular Aβ and synaptic dysfunction. Neuron 39:409-421.
101. Oddo S, Vasilevko V, Caccamo A, Kitazawa M, Cribbs DH, LaFerla FM (2006) Reduction of soluble Aβ and tau, but not soluble Aβ alone, ameliorates cognitive decline in transgenic mice with plaques and tangles. J Biol Chem 281:39413-39423.
102. Oddo S, Caccamo A, Tseng B, Cheng D, Vasilevko V, Cribbs DH, LaFerla FM (2008) Blocking Aβ42 accumulation delays the onset and progression of tau pathology via the C terminus of heat shock protein 70-interacting protein: a mechanistic link between Aβ and tau pathology. J Neurosci 28:12163-12175.
103. Palop JJ, Mucke L (2009) Epilepsy and cognitive impairments in Alzheimer disease. Arch Neurol 66:435-440.
104. Palop JJ, Chin J, Roberson ED, Wang J, Thwin MT, Bien-Ly N, Yoo J, Ho KO, Yu GQ, Kreitzer A, Finkbeiner S, Noebels JL, Mucke L (2007) Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease. Neuron 55:697-711.
105. Paquet D, Bhat R, Sydow A, Mandelkow EM, Berg S, Hellberg S, Falting J, Distel M, Koster RW, Schmid B, Haass C (2009) A zebrafish model of tauopathy allows in vivo imaging of neuronal cell death and drug evaluation. J Clin Invest 119:1382-1395.
106. Pei JJ, Sjogren M, Winblad B (2008) Neurofibrillary degeneration in Alzheimer's disease: from molecular mechanisms to identification of drug targets. Curr Opin Psychiatry 21:555-561.
107. Pennanen L, Welzl H, D'Adamo P, Nitsch RM, Götz J (2004) Accelerated extinction of conditioned taste aversion in P301L tau transgenic mice. Neurobiol Dis 15:500-509.
108. Pennanen L, Wolfer DP, Nitsch RM, Götz J (2006) Impaired spatial reference memory and increased exploratory behavior in P301L tau transgenic mice. Genes Brain Behav 5:369-379.
109. Pigino G, Morfini G, Atagi Y, Deshpande A, Yu C, Jungbauer L, LaDu M, Busciglio J, Brady S (2009) Disruption of fast axonal transport is a pathogenic mechanism for intraneuronal amyloid β. Proc Natl Acad Sci USA 106:5907-5912.
110. Probst A, Götz J, Wiederhold KH, Tolnay M, Mistl C, Jaton AL, Hong M, Ishihara T, Lee VM, Trojanowski JQ, Jakes R, Crowther RA, Spillantini MG, Burki K, Goedert M (2000) Axonopathy and amyotrophy in mice transgenic for human four-repeat tau protein. Acta Neuropathol (Berl) 99:469-481.
111. Ramsden M, Kotilinek L, Forster C, Paulson J, McGowan E, SantaCruz K, Guimaraes A, Yue M, Lewis J, Carlson G, Hutton M, Ashe KH (2005) Age-dependent neurofibrillary tangle formation, neuron loss, and memory impairment in a mouse model of human tauopathy (P301L). J Neurosci 25:10637-10647.
112. Rapoport M, Dawson HN, Binder LI, Vitek MP, Ferreira A (2002) Tau is essential to β-amyloid-induced neurotoxicity. Proc Natl Acad Sci USA 99:6364-6369.
113. Rezai-Zadeh K, Shytle D, Sun N, Mori T, Hou H, Jeanniton D, Ehrhart J, Townsend K, Zeng J, Morgan D, Hardy J, Town T, Tan J (2005) Green tea epigallocatechin-3-gallate (EGCG) modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice. J Neurosci 25:8807-8814.
114. Roberson ED, Scearce-Levie K, Palop JJ, Yan F, Cheng IH, Wu T, Gerstein H, Yu GQ, Mucke L (2007) Reducing endogenous tau ameliorates amyloid β-induced deficits in an Alzheimer's disease mouse model. Science 316:750-754.
115. Santacruz K, Lewis J, Spires T, Paulson J, Kotilinek L, Ingelsson M, Guimaraes A, DeTure M, Ramsden M, McGowan E, Forster C, Yue M, Orne J, Janus C, Mariash A, Kuskowski M, Hyman B, Hutton M, Ashe KH (2005) Tau suppression in a neurodegenerative mouse model improves memory function. Science 309:476-481.
116. Schenk D, Barbour R, Dunn W, Gordon G, Grajeda H, Guido T, Hu K, Huang J, Johnson-Wood K, Khan K, Kholodenko D, Lee M, Liao Z, Lieberburg I, Motter R, Mutter L, Soriano F, Shopp G, Vasquez N, Vandevert C, Walker S, Wogulis M, Yednock T, Games D, Seubert P (1999) Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400:173-177.
117. Schild A, Ittner LM, Götz J (2006) Altered phosphorylation of cytoskeletal proteins in mutant protein phosphatase 2A transgenic mice. Biochem Biophys Res Commun 343:1171-1178.
118. Selkoe DJ (2002) Alzheimer's disease is a synaptic failure. Science 298:789-791.
119. Shulman JM, Feany MB (2003) Genetic modifiers of tauopathy in Drosophila. Genetics 165:1233-1242.
120. Steinhilb ML, Dias-Santagata D, Fulga TA, Felch DL, Feany MB (2007) Tau phosphorylation sites work in concert to promote neurotoxicity in vivo. Mol Biol Cell 18:5060-5068.
121. Stokin GB, Lillo C, Falzone TL, Brusch RG, Rockenstein E, Mount SL, Raman R, Davies P, Masliah E, Williams DS, Goldstein LS (2005) Axonopathy and transport deficits early in the pathogenesis of Alzheimer's disease. Science 307:1282-1288.
122. Stokin GB, Almenar-Queralt A, Gunawardena S, Rodrigues EM, Falzone T, Kim J, Lillo C, Mount SL, Roberts EA, McGowan E, Williams DS, Goldstein LS (2008) Amyloid precursor protein-induced axonopathies are independent of amyloid-β peptides. Hum Mol Genet 17:3474-3486.
123. Sturchler-Pierrat C, Abramowski D, Duke M, Wiederhold KH, Mistl C, Rothacher S, Ledermann B, Burki K, Frey P, Paganetti PA, Waridel C, Calhoun ME, Jucker M, Probst A, Staufenbiel M, Sommer B (1997) Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. Proc Natl Acad Sci USA 94:13287-13292.
124. Su B, Wang X, Nunomura A, Moreira PI, Lee HG, Perry G, Smith MA, Zhu X (2008) Oxidative stress signaling in Alzheimer's disease. Curr Alzheimer Res 5:525-532.
125. Sugino K, Hempel CM, Miller MN, Hattox AM, Shapiro P, Wu C, Huang ZJ, Nelson SB (2006) Molecular taxonomy of major neuronal classes in the adult mouse forebrain. Nat Neurosci 9:99-107.
126. Tatsuta T, Langer T (2008) Quality control of mitochondria: protection against neurodegeneration and ageing. EMBO J 27:306-314.
127. Thal DR, Rub U, Orantes M, Braak H (2002) Phases of Aβ-deposition in the human brain and its relevance for the development of AD. Neurology 58:1791-1800.
128. Thies E, Mandelkow EM (2007) Missorting of tau in neurons causes degeneration of synapses that can be rescued by the kinase MARK2/Par-1. J Neurosci 27:2896-2907.
129. Van Dam D, De Deyn PP (2006) Drug discovery in dementia: the role of rodent models. Nat Rev Drug Discov 5:956-970.
130. van de Hoef DL, Hughes J, Livne-Bar I, Garza D, Konsolaki M, Boulianne GL (2009) Identifying genes that interact with Drosophila presenilin and amyloid precursor protein. Genesis 47:246-260.
131. Wang J, Farr GW, Hall DH, Li F, Furtak K, Dreier L, Horwich AL (2009) An ALS-linked mutant SOD1 produces a locomotor defect associated with aggregation and synaptic dysfunction when expressed in neurons of Caenorhabditis elegans. PLoS Genet 5:e1000350.
132. Wittmann CW, Wszolek MF, Shulman JM, Salvaterra PM, Lewis J, Hutton M, Feany MB (2001) Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles. Science 293:711-714.
133. Yankner BA, Lu T (2009) Amyloid β-protein toxicity and the pathogenesis of Alzheimer disease. J Biol Chem 284:4755-4759.
134. Zilka N, Filipcik P, Koson P, Fialova L, Skrabana R, Zilkova M, Rolkova G, Kontsekova E, Novak M (2006) Truncated tau from sporadic Alzheimer's disease suffices to drive neurofibrillary degeneration in vivo. FEBS Lett 580:3582-3588.