Nature, nurture and neurology: Gene-environment interactions in neurodegenerative disease. FEBS Anniversary Prize Lecture delivered on 27 June 2004 at the 29th FEBS Congress in Warsaw

FEBS Journal

Volumn 272, Issue 10, 2005, Pages 2347-2361

  Spires, Tara L ^a   Hannan, Anthony J ^b  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

Alzheimer; BDNF; Environmental enrichment; Huntington; Neurodegeneration

Indexed keywords

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL MODEL; COGNITIVE DEFECT; CONFERENCE PAPER; CONTROLLED STUDY; DEGENERATIVE DISEASE; DISEASE COURSE; ENVIRONMENTAL ENRICHMENT; ENVIRONMENTAL FACTOR; EPIGENETICS; GENE EXPRESSION; GENE EXPRESSION PROFILING; HEREDITY; HUMAN; HUNTINGTON CHOREA; MOTOR DYSFUNCTION; MOUSE; NERVE CELL PLASTICITY; NERVE DEGENERATION; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; PARKINSON DISEASE; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN INTERACTION; SIGNAL TRANSDUCTION; SYNAPTIC TRANSMISSION; TRANSCRIPTION REGULATION; TRANSGENE; TRANSGENIC MOUSE;

ANIMALS; BEHAVIOR, ANIMAL; BRAIN-DERIVED NEUROTROPHIC FACTOR; ENVIRONMENT; EPIGENESIS, GENETIC; HUMANS; MICE; MICE, TRANSGENIC; NEURODEGENERATIVE DISEASES; PHENOTYPE; SYNAPSES; TRANSCRIPTION, GENETIC;

ANIMALIA; MUS MUSCULUS;

EID: 18944393305     PISSN: 1742464X     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1742-4658.2005.04677.x     Document Type: Conference Paper

References (144)

1. Bates G, Harper P & Jones L (2002) Huntington's Disease, 3rd edn. Oxford University Press, Oxford.
2. Glass M, Dragunow M & Faull RL (2000) The pattern of neurodegeneration in Huntington's disease: a comparative study of cannabinoid, dopamine, adenosine and GABA (A) receptor alterations in the human basal ganglia in Huntington's disease. Neuroscience 97, 505-519.
3. DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, Vonsattel JP & Aronin N (1997) Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277, 1990-1993.
4. Gusella JF, Wexler NS, Conneally PM, Naylor SL, Anderson MA, Tanzi RE, Watkins PC, Ottina K, Wallace MR, Sakaguchi AY et al. (1983) A polymorphic DNA marker genetically linked to Huntington's disease. Nature 306, 234-238.
5. Huntington's Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72, 971-983.
6. Young AB (2003) Huntingtin in health and disease. J Clin Invest 111, 299-302.
7. Andrew SE, Goldberg YP, Kremer B, Telenius H, Theilmann J, Adam S, Starr E, Squitieri F, Lin B, Kalchman MA et al. (1993) The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease. Nat Genet 4, 398-403.
8. Rosenblatt A, Brinkman RR, Liang KY, Almqvist EW, Margolis RL, Huang CY, Sherr M, Franz ML, Abbott MH, Hayden MR et al. (2001) Familial influence on age of onset among siblings with Huntington disease. Am J Med Genet 105, 399-403.
9. MacDonald ME, Vonsattel JP, Shrinidhi J, Couropmitree NN, Cupples LA, Bird ED, Gusella JF & Myers RH (1999) Evidence for the GluR6 gene associated with younger onset age of Huntington's disease. Neurology 53, 1330-1332.
10. Rubinsztein DC, Leggo J, Chiano M, Dodge A, Norbury G, Rosser E & Craufurd D (1997) Genotypes at the GluR6 kainate receptor locus are associated with variation in the age of onset of Huntington disease. Proc Natl Acad Sci USA 94, 3872-3876.
11. Kehoe P, Krawczak M, Harper PS, Owen MJ & Jones AL (1999) Age of onset in Huntington disease: sex specific influence of apolipoprotein E genotype and normal CAG repeat length. J Med Genet 36, 108-111.
12. Holbert S, Denghien I, Kiechle T, Rosenblatt A, Wellington C, Hayden MR, Margolis RL, Ross CA, Dausset J, Ferrante RJ et al. (2001) The Gln-Ala repeat transcriptional activator CA150 interacts with huntingtin: neuropathologic and genetic evidence for a role in Huntington's disease pathogenesis. Proc Natl Acad Sci USA 98, 1811-1816.
13. van Dellen A & Hannan AJ (2004) Genetic and environmental factors in the pathogenesis of Huntington's disease. Neurogenetics 5, 9-17.
14. Mangiarini L, Sathasivam K, Seller M, Cozens B, Harper A, Hetherington C, Lawton M, Trottier Y, Lehrach H, Davies SW et al. (1996) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87, 493-506.
15. Davies SW, Turmaine M, Cozens BA, DiFiglia M, Sharp AH, Ross CA, Scherzinger E, Wanker EE, Mangiarini L & Bates GP (1997) Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 90, 537-548.
16. Dunnett SB, Carter RJ, Watts C, Torres EM, Mahal A, Mangiarini L, Bates G & Morton AJ (1998) Striatal transplantation in a transgenic mouse model of Huntington's disease. Exp Neurol 154, 31-40.
17. Sathasivam K, Hobbs C, Mangiarini L, Mahal A, Turmaine M, Doherty P, Davies SW & Bates GP (1999) Transgenic models of Huntington's disease. Philos Trans R Soc Lond B Sci 354, 963-969.
18. Lione LA, Carter RJ, Hunt MJ, Bates GP, Morton AJ & Dunnett SB (1999) Selective discrimination learning impairments in mice expressing the human Huntington's disease mutation. J Neurosci 19, 10428-10437.
19. Carter RJ, Lione LA, Humby T, Mangiarini L, Mahal A, Bates GP, Dunnett SB & Morton AJ (1999) Characterization of progressive motor deficits in mice transgenic for the human Huntington's disease mutation. J Neurosci 19, 3248-3257.
20. Murphy KP, Carter RJ, Lione LA, Mangiarini L, Mahal A, Bates GP, Dunnett SB & Morton AJ (2000) Abnormal synaptic plasticity and impaired spatial cognition in mice transgenic for exon 1 of the human Huntington's disease mutation. J Neurosci 20, 5115-5123.
21. Bennett DA, Diamond MC, Krech D & Rosenzweig MR (1964) Chemical and anatomical plasticity of brain. Science 146, 610-619.
22. Frick KM, Stearns NA, Pan JY & Berger-Sweeney J (2003) Effects of environmental enrichment on spatial memory and neurochemistry in middle-aged mice. Learn Mem 10, 187-198.
23. Frick KM & Fernandez SM (2003) Enrichment enhances spatial memory and increases synaptophysin levels in aged female mice. Neurobiol Aging 24, 615-626.
24. Duffy SN, Craddock KJ, Abel T & Nguyen PV (2001) Environmental enrichment modifies the PKA-dependence of hippocampal LTP and improves hippocampus-dependent memory. Learn Mem 8, 26-34.
25. Williams BM, Luo Y, Ward C, Redd K, Gibson R, Kuczaj SA & McCoy JG (2001) Environmental enrichment: effects on spatial memory and hippocampal CREB immunoreactivity. Physiol Behav 73, 649-658.
26. Kempermann G, Kuhn HG & Gage FH (1997) More hippocampal neurons in adult mice living in an enriched environment. Nature 386, 493-495.
27. Fiala B, Snow FM & Greenough WT (1977) 'Impoverished' rats weigh more than 'enriched' rats because they eat more. Devel Psychobiol 10, 537-541.
28. Churchill JD, Galvez R, Colcombe S, Swain RA, Kramer AF & Greenough WT (2002) Exercise, experience and the aging brain. Neurobiol Aging 23, 941-955.
29. Nithianantharajah J, Levis H & Murphy M (2004) Environmental enrichment results in cortical and subcortical changes in levels of synaptophysin and PSD-95 proteins. Neurobiol Learn Mem 81, 200-210.
30. Altman J & Das GD (1965) Post-natal origin of microneurones in the rat brain. Nature 207, 953-956.
31. Gould E & Gross CG (2002) Neurogenesis in adult mammals: some progress and problems. J Neurosci 22, 619-623.
32. Young DH, Lawlor PA, Leone P, Dragunow M & During MJ (1999) Environmental enrichment inhibits spontaneous apoptosis, prevents seizures and is neuroprotective. Nat Med 5, 448-453.
33. Kempermann G, Wiskott L & Gage FH (2004) Functional significance of adult neurogenesis. Curr Opin Neurobiol 14, 186-191.
34. Rampon C, Jiang CH, Dong H, Tang YP, Lockhart DJ, Schultz PG, Tsien JZ & Hu Y (2000) Effects of environmental enrichment on gene expression in the brain. Proc Natl Acad Sci USA 97, 12880-12884.
35. Falkenberg T, Mohammed AK, Henriksson B, Persson H, Winblad B & Lindefors N (1992) Increased expression of brain-derived neurotrophic factor mRNA in rat hippocampus is associated with improved spatial memory and enriched environment. Neurosci Lett 138, 153-156.
36. Pham TM, Ickes B, Albeck D, Soderstrom S, Granholm AC & Mohammed AH (1999) Changes in brain nerve growth factor levels and nerve growth factor receptors in rats exposed to environmental enrichment for one year. Neuroscience 94, 279-286.
37. Zhao LR, Risedal A, Wojcik A, Hejzlar J, Johansson BB & Kokaia Z (2001) Enriched environment influences brain-derived neurotrophic factor levels in rat forebrain after focal stroke. Neurosci Lett 305, 169-172.
38. Keyvani K, Sachser N, Witte OW & Paulus W (2004) Gene expression profiling in the intact and injured brain following environmental enrichment. J Neuropathol Exp Neurol 63, 598-609.
39. Sale A, Putignano E, Cancedda L, Landi S, Cirulli F, Berardi N & Maffei L (2004) Enriched environment and acceleration of visual system development. Neuropharmacology 47, 649-660.
40. Cancedda L, Putignano E, Sale A, Viegi A, Berardi N & Maffei L (2004) Acceleration of visual system development by environmental enrichment. J Neurosci 24, 4840-4848.
41. Bartoletti A, Medini P, Berardi N & Maffei L (2004) Environmental enrichment prevents effects of dark-rearing in the rat visual cortex. Nat Neurosci 7, 215-216.
42. Guilarte TR, Toscano CD, McGlothan JL & Weaver SA (2003) Environmental enrichment reverses cognitive and molecular deficits induced by developmental lead exposure. Ann Neurol 53, 50-56.
43. Pinaud R, Penner MR, Robertson HA & Currie RW (2001) Upregulation of the immediate early gene arc in the brains of rats exposed to environmental enrichment: implications for molecular plasticity. Brain Res Mol Brain Res 91, 50-56.
44. Pinaud R, Tremere LA, Penner MR, Hess FF, Robertson HA & Currie RW (2002) Complexity of sensory environment drives the expression, of candidate-plasticity gene, nerve growth factor induced-A. Neuroscience 112, 573-582.
45. Goto S, Radak Z, Nyakas C, Chung HY, Naito H, Takahashi R, Nakamoto H & Abea R (2004) Regular exercise: an effective means to reduce oxidative stress in old rats. Ann N Y Acad Sci 1019, 471-474.
46. Kitamura T, Mishina M & Sugiyama H (2003) Enhancement of neurogenesis by running wheel exercises is suppressed in mice lacking NMDA receptor epsilon 1 subunit. Neurosci Res 47, 55-63.
47. Rhodes JS, van Praag H, Jeffrey S, Girard I, Mitchell GS, Garland T & Gage FH (2003) Exercise increases hippocampal neurogenesis to high levels but does not improve spatial learning in mice bred for increased voluntary wheel running. Behav Neurosci 117, 1006-1016.
48. Farmer J, Zhao X, van Praag H, Wodtke K, Gage FH & Christie BR (2004) Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo. Neuroscience 124, 71-79.
49. van Dellen A, Blakemore C, Deacon R, York D & Hannan AJ (2000) Delaying the onset of Huntington's in mice. Nature 404, 721-722.
50. Spires TL, Varshney N, Grote H, van Dellen A, Blakemore C & Hannan AJ (2002) Effects of environmental enrichment on disease symptoms, gene expression and protein aggregation in Huntington's disease mice. Soc Neurosci Abstr 28, 388.13.
51. Hockly E, Cordery PM, Woodman B, Mahal A, van Dellen A, Blakemore C, Lewis CM, Hannan AJ & Bates GP (2002) Environmental enrichment slows disease progression in R6/2 Huntington's disease mice. Ann Neurol 51, 235-242.
52. Schilling G, Savonenko AV, Coonfield ML, Morton JL, Vorovich E, Gale A, Neslon C, Chan N, Eaton M, Fromholt D et al. (2004) Environmental, pharmacological, and genetic modulation of the HD phenotype in transgenic mice. Exp Neurol 187, 137-149.
53. Sullivan FR, Bird ED, Alpay M & Cha JH (2001) Remotivation therapy and Huntington's disease. J Neurosci Nurs 33, 136-142.
54. Georgiou N, Bradshaw JL, Chiu E, Tudor A, O'Gorman L & Phillips JG (1999) Differential clinical and motor control function in a pair of monozygotic twins with Huntington's disease. Mov Disord 14, 320-325.
55. Wexler NS, Lorimer J, Porter J, Gomez F, Moskowitz C, Shackell E, Marder K, Penchaszadeh G, Roberts SA, Gayan J et al. (2004) Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset. Proc Natl Acad Sci USA 101, 3498-3503.
56. van Dellen A, Deacon R, York D, Blakemore C & Hannan AJ (2001) Anterior cingulate cortical transplantation in transgenic Huntington's disease mice. Brain Res Bull 56, 313-318.
57. Spires TL, Grote HE, Varshney NK, Cordery PM, Van Dellen A, Blakemore C & Hannan AJ (2004) Environmental enrichment rescues protein deficits in a mouse model of Huntington's disease, indicating a possible disease mechanism. J Neurosci 24, 2270-2276.
58. Altar CA, Cai N, Bliven T, Juhasz M, Conner JM, Acheson AL, Lindsay RM & Wiegand SJ (1997) Anterograde transport of brain-derived neurotrophic factor and its role in the brain. Nature 389, 856-860.
59. Zuccato C, Ciammola A, Rigamonti D, Leavitt BR, Goffredo D, Conti L, MacDonald ME, Friedlander RM, Silani V, Hayden MR et al. (2001) Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease. Science 293, 493-498.
60. Ferrer I, Goutan E, Marin C, Rey MJ & Ribalta T (2000) Brain-derived neurotrophic factor in Huntington disease. Brain Res 866, 257-261.
61. Luthi-Carter R, Hanson SA, Strand AD, Bergstrom DA, Chun W, Peters NL, Woods AM, Chan EY, Kooperberg C, Krainc D et al. (2002) Dysregulation of gene expression in the R6/2 model of polyglutamine disease: parallel changes in muscle and brain. Hum Mol Genet 11, 1911-1926.
62. Duan W, Guo Z, Jiang H, Ware M, Li XJ & Mattson MP (2003) Dietary restriction normalizes glucose metabolism and BDNF levels, slows disease progression, and increases survival in huntingtin mutant mice. Proc Natl Acad Sci USA 100, 2911-2916.
63. Clifford JJ, Drago J, Natoli AL, Wong JY, Kinsella A, Waddington JL & Vaddadi KS (2002) Essential fatty acids given from conception prevent topographies of motor deficit in a transgenic model of Huntington's disease. Neuroscience 109, 81-88.
64. Lee J, Duan W, Long JM, Ingram DK & Mattson MP (2000) Dietary restriction increases the number of newly generated neural cells, and induces BDNF expression, in the dentate gyrus of rats. J Mol Neurosci 15, 99-108.
65. Barnabe-Heider F & Miller FD (2003) Endogenously produced neurotrophins regulate survival and differentiation of cortical progenitors via distinct signaling pathways. J Neurosci 23, 5149-5160.
66. Lazic SE, Grote H, Armstrong RJ, Blakemore C, Hannan AJ, van Dellen A & Barker RA (2004) Decreased hippocampal cell proliferation in R6/1 Huntington's mice. Neuroreport 15, 811-813.
67. van Praag H, Kempermann G & Gage FH (2000) Neural consequences of environmental enrichment. Nat Rev Neurosci 1, 191-198.
68. Grote HE, Howard ML, van Dellen A, Blakemore C & Hannan AJ (2005) The serotonin reuptake inhibitor fluoxetine rescues cognitive and affective deficits in a transgenic mouse model of Huntington's disease. Proc Aust Neurosci Soc 16, 131.
69. Curtis MA, Penney EB, Pearson AG, van Roon-Mom WM, Butterworth NJ, Dragunow M, Connor B & Faull RL (2003) Increased cell proliferation and neurogenesis in the adult human Huntington's disease brain. Proc Natl Acad Sci USA 100, 9023-9027.
70. Luthi-Carter R, Strand A, Peters NL, Solano SM, Hollingsworth ZR, Menon AS, Frey AS, Spektor BS, Penney EB, Schilling G et al. (2000) Decreased expression of striatal signaling genes in a mouse model of Huntington's disease. Hum Mol Genet 9, 1259-1271.
71. Chan EY, Luthi-Carter R, Strand A, Solano SM, Hanson SA, DeJohn MM, Kooperberg C, Chase KO, DiFiglia M, Young AB et al. (2002) Increased huntingtin protein length reduces the number of polyglutamine-induced gene expression changes in mouse models of Huntington's disease. Hum Mol Genet 11, 1939-1951.
72. Cha JH, Kosinski CM, Kerner JA, Alsdorf SA, Mangiarini L, Davies SW, Penney JB, Bates GP & Young AB (1998) Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human huntington disease gene. Proc Natl Acad Sci USA 95, 6480-6485.
73. van Dellen A, Welch J, Dixon RM, Cordery P, York D, Styles P, Blakemore C & Hannan AJ (2000) N-Acetylaspartate and DARPP-32 levels decrease in the corpus striatum of Huntington's disease mice. Neuroreport 11, 3751-3757.
74. Glass M, van Dellen A, Blakemore C, Hannan AJ & Faull RL (2004) Delayed onset of Huntington's disease in mice in an enriched environment correlates with delayed loss of cannabinoid CB1 receptors. Neuroscience 123, 207-212.
75. Hannan AJ (2004) Huntington's disease: which drugs might help patients? IDrugs 7, 351-358.
76. Hannan AJ (2004) Molecular mediators, environmental modulators and experience-dependent synaptic dysfunction in Huntington's disease. Acta Biochim Pol 51, 415-430.
77. Spires TL, Grote HE, Garry S, Cordery PM, Van Dellen A, Blakemore C & Hannan AJ (2004) Dendritic spine pathology and deficits in experience-dependent dendritic plasticity in R6/1 Huntington's disease transgenic mice. Eur J Neurosci 19, 2799-2807.
78. Levine MS, Klapstein GJ, Koppel A, Gruen E, Cepeda C, Vargas ME, Jokel ES, Carpenter EM, Zanjani H, Hurst RS et al. (1999) Enhanced sensitivity to N-methyl-D-aspartate receptor activation in transgenic and knockin mouse models of Huntington's disease. J Neurosci Res 58, 515-532.
79. Laforet GA, Sapp E, Chase K, McIntyre C, Boyce FM, Campbell M, Cadigan BA, Warzecki L, Tagle DA, Reddy PH et al. (2001) Changes in cortical and striatal neurons predict behavioral and electrophysiological abnormalities in a transgenic murine model of Huntington's disease. J Neurosci 21, 9112-9123.
80. Cepeda C, Ariano MA, Calvert CR, Flores-Hernandez J, Chandler SH, Leavitt BR, Hayden MR & Levine MS (2001) NMDA receptor function in mouse models of Huntington disease. J Neurosci Res 66, 525-539.
81. Cepeda C, Hurst RS, Calvert CR, Hernandez-Echeagaray E, Nguyen OK, Jocoy E, Christian LJ, Ariano MA & Levine MS (2003) Transient and progressive electrophysiological alterations in the corticostriatal pathway in a mouse model of Huntington's disease. J Neurosci 23, 961-969.
82. Mazarakis NK, Cybulska-Klosowicz A, Grote H, Pang T, Van Dellen A, Kossut M, Blakemore C & Hannan AJ (2005) Experience-dependent cortical plasticity and sensory discrimination deficits in presymptomatic Huntington's disease mice. J Neurosci 25, 3059-3066.
83. Cybulska-Klosowicz A, Mazarakis NK, Van Dellen A, Kossut M, Blakemore C, Hannan AJ & Kossut M (2004) Impaired learning-dependent cortical plasticity in Huntington's disease transgenic mice. Neurobiol Dis 17, 427-434.
84. Hebert LE, Scherr PA, Bienias JL, Bennett DA & Evans DA (2003) Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol 60, 1119-1122.
85. Citron M, Oltersdorf T, Haass C, McConlogue L, Hung AY, Seubert P, Vigo-Pelfrey C, Lieberburg I & Selkoe DJ (1992) Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production. Nature 360, 672-674.
86. Alzheimer A (1907) Ubereine eigenartige Erkrankung der Hirnrinde. Allg Z Psychiatr - Gerichtl Med 64, 146-148.
87. Spires TL & Hyman BT (2004) Neuronal structure is altered by amyloid plaques. Rev Neurosci 15, 267-278.
88. Glenner GG & Wong CW (1984) Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120, 885-890.
89. Small DH, Mok SS & Bornstein JC (2001) Alzheimer's disease and Abeta toxicity: from top to bottom. Nat Rev Neurosci 2, 595-598.
90. 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.
91. Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L et al. (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 349, 704-706.
92. Naruse S, Igarashi S, Kobayashi H, Aoki K, Inuzuka T, Kaneko K, Shimizu T, Iihara K, Kojima T, Miyatake T et al. (1991) Mis-sense mutation Val-Ile in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's disease. Lancet 337, 978-979.
93. De Strooper B (2003) Aph-1, Pen-2, and Nicastrin with Presenilin generate an active gamma-Secretase complex. Neuron 38, 9-12.
94. Selkoe DJ (1999) Biology of beta-amyloid precursor protein and the mechanism of Alzheimer disease. In Alzheimer Disease (Terry RD, Katzman R, Bick KL & Sisoda SS, eds), pp. 293-310, Lippincott Williams & Wilkins, Philadelphia.
95. Alzheimer's Disease Collaborative Group (1995) The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families. Nat Genet 11, 219-222.
96. Levy-Lahad E, Wijsman EM, Nemens E, Anderson L, Goddard KA, Weber JL, Bird TD & Schellenberg GD (1995) A familial Alzheimer's disease locus on chromosome 1. Science 269, 970-973.
97. Rogaev EI, Sherrington R, Rogaeva EA, Levesque G, Ikeda M, Liang Y, Chi H, Lin C, Holman K, Tsuda T et al. (1995) Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature 376, 775-778.
98. Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K et al. (1995) Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature 375, 754-760.
99. St George-Hyslop P, Haines J, Rogaev E, Mortilla M, Vaula G, Pericak-Vance M, Foncin JF, Montesi M, Bruni A, Sorbi S et al. (1992) Genetic evidence for a novel familial Alzheimer's disease locus on chromosome 14. Nat Genet 2, 330-334.
100. Kidd M (1963) Paired helical filaments in electron microscopy in Alzheimer's disease. Nature 197, 192-193.
101. Brion JP, Couck AM, Passareiro E & Flament-Durand J (1985) Neurofibrillary tangles of Alzheimer's disease: an immunohistochemical study. J Submicrosc Cytol 17, 89-96.
102. Foster NL, Wilhelmsen K, Sima AA, Jones MZ, D'Amato CJ & Gilman S (1997) Frontotemporal dementia and parkinsonism linked to chromosome 17: a consensus conference. Conference Participants. Ann Neurol 41, 706-715.
103. 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.
104. Saunders AM, Strittmatter WJ, Schmechel D, George-Hyslop PH, Pericak-Vance MA, Joo SH, Rosi BL, Gusella JF, Crapper-MacLachlan DR, Alberts MJ et al. (1993) Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. Neurology 43, 1467-1472.
105. Corder EH, Saunders AM, Risch NJ, Strittmatter WJ, Schmechel DE, Gaskell PC, Rimmler JB, Locke PA, Conneally PM, Schmader KE et al. (1994) Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nat Genet 7, 180-184.
106. Phinney AL, Horne P, Yang J, Janus C, Bergeron C & Westaway D (2003) Mouse models of Alzheimer's disease: the long and filamentous road. Neurol Res 25, 590-600.
107. Chapman PF, White GL, Jones MW, Cooper-Blacketer D, Marshall VJ, Irizarry M, Younkin L, Good MA, Bliss TV, Hyman BT et al. (1999) Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice. Nat Neurosci 2, 271-276.
108. Mortimer JA, van Duijn CM, Chandra V, Fratiglioni L, Graves AB, Heyman A, Jorm AF, Kokmen E, Kondo K, Rocca WA et al. (1991) Head trauma as a risk factor for Alzheimer's disease: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. Int. J Epidemiol 20, S28-S35.
109. Rasmusson DX, Brandt J, Martin DB & Folstein MF (1995) Head injury as a risk factor in Alzheimer's disease. Brain Inj 9, 213-219.
110. Uryu K, Laurer H, McIntosh T, Pratico D, Martinez D, Leight S, Lee VM & Trojanowski JQ (2002) Repetitive mild brain trauma accelerates Abeta deposition, lipid peroxidation, and cognitive impairment in a transgenic mouse model of Alzheimer amyloidosis. J Neurosci 22, 446-454.
111. Mayeux R, Ottman R, Maestre G, Ngai C, Tang MX, Ginsberg H, Chun M, Tycko B & Shelanski M (1995) Synergistic effects of traumatic head injury and apolipoprotein-epsilon 4 in patients with Alzheimer's disease. Neurology 45, 555-557.
112. Laurin D, Verreault R, Lindsay J, MacPherson K & Rockwood K (2001) Physical activity and risk of cognitive impairment and dementia in elderly persons. Arch Neurol 58, 498-504.
113. Scarmeas N, Levy G, Tang MX, Manly J & Stern Y (2001) Influence of leisure activity on the incidence of Alzheimer's disease. Neurology 57, 2236-2242.
114. Stern Y, Gurland B, Tatemichi TK, Tang MX, Wilder D & Mayeux R (1994) Influence of education and occupation on the incidence of Alzheimer's disease. JAMA 271, 1004-1010.
115. Wilson RS, Bennett DA, Bienias JL, Aggarwal NT, Mendes de Leon CF, Morris MC, Schneider JA & Evans DA (2002) Cognitive activity and incident AD in a population-based sample of older persons. Neurology 59, 1910-1914.
116. Wilson RS, Mendes De Leon CF, Barnes LL, Schneider JA, Bienias JL, Evans DA & Bennett DA (2002) Participation in cognitively stimulating activities and risk of incident Alzheimer disease. JAMA 287, 742-748.
117. Friedland RP, Fritsch T, Smyth KA, Koss E, Lerner AJ, Chen CH, Petot GJ & Debanne SM (2001) Patients with Alzheimer's disease have reduced activities in midlife compared with healthy control-group members. Proc Natl Acad Sci USA 98, 3440-3445.
118. Scarmeas N & Stern Y (2004) Cognitive reserve: implications for diagnosis and prevention of Alzheimer's disease. Curr Neurol Neurosci Rep 4, 374-380.
119. Luchsinger JA & Mayeux R (2004) Dietary factors and Alzheimer's disease. Lancet Neurol 3, 579-587.
120. Standridge JB (2004) Pharmacotherapeutic approaches to the prevention of Alzheimer's disease. Am J Geriatr Pharmacother 2, 119-132.
121. Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Wilson RS, Aggarwal N & Schneider J (2003) Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol 60, 940-946.
122. Mattson MP (2003) Gene-diet interactions in brain aging and neurodegenerative disorders. Ann Intern Med 139, 441-444.
123. Berman K & Brodaty H (2004) Tocopherol (vitamin E) in Alzheimer's disease and other neurodegenerative disorders. CNS Drugs 18, 807-825.
124. McDowell I (2001) Alzheimer's disease: insights from epidemiology. Aging (Milano) 13, 143-162.
125. Luchsinger JA, Tang MX, Shea S & Mayeux R (2002) Caloric intake and the risk of Alzheimer disease. Arch Neurol 59, 1258-1263.
126. Breteler MM (2000) Vascular risk factors for Alzheimer's disease: An epidemiologic perspective. Neurobiol Aging 21, 153-160.
127. Miller LJ & Chacko R (2004) The role of cholesterol and statins in Alzheimer's disease. Ann Pharmacother 38, 91-98.
128. Arendash GW, Garcia MF, Costa DA, Cracchiolo JR, Wefes IM & Potter H (2004) Environmental enrichment improves cognitive function in aged Alzheimer's transgenic mice despite stable [beta]-amyloid deposition. Neuroreport 15, 1751-1754.
129. Cracchiolo JR, Costa DA, Arendash GW, Bales KR, Paul SM & Potter H (2004) Environmental enrichment in Alzheimer's transgenic mice protects against widespread cognitive impairment without affecting Aβ deposition. Soc Neurosci Abstr 30, 830.11.
130. Jankowsky JL, Xu G, Fromholt D, Gonzales V & Borchelt DR (2003) Environmental enrichment exacerbates amyloid plaque formation in a transgenic mouse model of Alzheimer disease. J Neuropathol Exp Neurol 62, 1220-1227.
131. Levi O, Jongen-Relo AL, Feldon J, Roses AD & Michaelson DM (2003) ApoE4 impairs hippocampal plasticity isoform-specifically and blocks the environmental stimulation of synaptogenesis and memory. Neurobiol Dis 13, 273-282.
132. Lazarov O, Robinson J, Tang Y-P, Hairston IS, Korade-Mirnics Z, Lee VM-Y, Hersh LB, Sapolsky RM, Mirnics K & Sidodia SS (2005) Environmental enrichment reduces Aβ levels and amyloid deposition in transgenic mice. Cell 120, 101-113.
133. Olazaran J, Muniz R, Reisberg B, Pena-Casanova J, delSer T, Cruz-Jentoft AJ, Serrano P, Navarro E, Garcia de la Rocha ML, Frank A et al. (2004) Benefits of cognitive-motor intervention in MCI and mild to moderate Alzheimer disease. Neurology 63, 2348-2353.
134. Le Couleur DG, Muller M, Yang MC, Mellick GD & McLean AJ (2002) Age-environment and gene-environment interactions in the pathogenesis of Parkinson's disease. Rev Environ Health 17, 51-64.
135. Huang Y, Cheung L, Rowe D & Halliday G (2004) Genetic contributions to Parkinson's disease. Brain Res Brain Res Rev 46, 44-70.
136. Tanner CM, Ottman R, Goldman SM, Ellenberg J, Chan P, Mayeux R & Langston JW (1999) Parkinson disease in twins: an etiologic study. JAMA 281, 341-346.
137. Paolini M, Sapone A & Gonzalez FJ (2004) Parkinson's disease, pesticides and individual vulnerability. Trends Pharmacol Sci 25, 124-129.
138. Betarbet R, Sherer TB, Mackenzie G, Garcia-Osuna M, Panov AV & Greenamyre JT (2000) Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nature Neurosci 3, 1301-1306.
139. Dauer W & Przedborski S (2003) Parkinson's Disease: mechanisms and models. Neuron 39, 889-909.
140. Ascherio A & Chen H (2003) Caffeinated clues from epidemiology of Parkinson's disease. Neurology 61, 51S-54.
141. Morens DM, Grandinetti A, Reed D, White LR & Ross GW (1995) Cigarette smoking and protection from Parkinson's disease: false association or etiologic clue? Neurology 45, 1041-1051.
142. Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV & Greenamyre JT (2000) Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci 3, 1301-1306.
143. Priyadarshi A, Khuder SA, Schaub EA & Shrivastava S (2000) A meta-analysis of Parkinson's disease and exposure to pesticides. Neurotoxicology 21, 435-440.
144. Mayeux R (2003) Epidemiology of neurodegeneration. Annu Rev Neurosci 26, 81-104.