Changing perspectives on alzheimer's disease: Thinking outside the amyloid box

Journal of Alzheimer's Disease

Volumn 25, Issue 4, 2011, Pages 571-581

  D'Alton, Simon ^a   George, Daniel R ^b  

^a UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^b PENN STATE COLLEGE OF MEDICINE   (United States)

Author keywords

Alzheimer's disease; amyloid; health; hypoxia; metabolism; oxidative stress; public risk factors; therapeutics

Indexed keywords

AMYLOID BETA PROTEIN;

AGING; ALZHEIMER DISEASE; ARTICLE; HEALTH PROGRAM; HUMAN; NEUROPROTECTION; PRIORITY JOURNAL; PUBLIC HEALTH; RISK FACTOR; SOCIAL ASPECT; STRESS;

EID: 79960699477     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-2011-110089     Document Type: Article

References (116)

1. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297, 353-356. (Pubitemid 34790756)
2. Cirrito JR, Yamada KA, Finn MB, Sloviter RS, Bales KR, May PC, Schoepp DD, Paul SM, Mennerick S, Holtz-man DM (2005) Synaptic activity regulates interstitial fluid amyloid-beta levels in vivo. Neuron 48, 913-922. (Pubitemid 41814696)
3. Kamenetz F, Tomita T, Hsieh H, Seabrook G, Borchelt D, Iwatsubo T, Sisodia S, Malinow R (2003) APP processing and synaptic function. Neuron 37, 925-937. (Pubitemid 36398299)
4. Puzzo D, Privitera L, Leznik E, Fa M, Staniszewski A, Palmeri A, Arancio O (2008) Picomolar amyloid-beta positively modulates synaptic plasticity and memory in hippocampus. J Neurosci 28, 14537-14545.
5. Bertram L, Lill CM, Tanzi RE (2010) The genetics of Alzheimer disease: back to the future. Neuron 68, 270-281.
6. Janson J, Laedtke T, Parisi JE, O'Brien P, Petersen RC, Butler PC (2004) Increased risk of type 2 diabetes in Alzheimer disease. Diabetes 53, 474-481. (Pubitemid 38174565)
7. Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM (1999) Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology 53, 1937-1942.
8. Xu W, Qiu C, Winblad B, Fratiglioni L (2007) The effect of borderline diabetes on the risk of dementia and Alzheimer's disease. Diabetes 56, 211-216.
9. Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P (2006) Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol 5, 64-74. (Pubitemid 41790697)
10. Peers C, Dallas ML, Boycott HE, Scragg JL, Pearson HA, Boyle JP (2009) Hypoxia and neurodegeneration. Ann N Y Acad Sci 1177, 169-177.
11. Altieri M, DiPiero V, Pasquini M, Gasparini M, Vanacore N, Vicenzini E, Lenzi GL (2004) Delayed poststroke dementia: a 4-year follow-up study. Neurology 62, 2193-2197. (Pubitemid 38787774)
12. Guo Z, Cupples LA, Kurz A, Auerbach SH, Volicer L, Chui H, Green RC, Sadovnick AD, Duara R, DeCarli C, Johnson K, Go RC, Growdon JH, Haines JL, Kukull WA, Farrer LA (2000) Head injury and the risk of AD in the MIRAGE study. Neurology 54, 1316-1323. (Pubitemid 30174053)
13. Rusanen M, Kivipelto M, Quesenberry CP Jr, Zhou J, Whitmer RA (2011) Heavy smokinginmidlife and long-term risk of Alzheimer disease and vascular dementia. Arch Intern Med 171, 333-339.
14. Kivipelto M, Ngandu T, Fratiglioni L, Viitanen M, Kareholt I, Winblad B, Helkala EL, Tuomilehto J, Soininen H, Nissi-nen A (2005) Obesity and vascular risk factorsat midlife and the risk of dementia and Alzheimer disease. Arch Neurol 62, 1556-1560. (Pubitemid 41434560)
15. Keller L, Xu W, Wang HX, Winblad B, Fratiglioni L, Graff C (2011) The obesity related gene, FTO, interacts with APOE, and is associated with Alzheimer's disease risk: a prospective cohort study. J Alzheimers Dis 23, 461-469.
16. Hayden KM, Norton MC, Darcey D, Ostbye T, Zandi PP, Breitner JC, Welsh-Bohmer KA (2010) Occupational exposure to pesticides increases the risk of incident AD: the Cache County study. Neurology 74, 1524-1530.
17. Zambon D, Quintana M, Mata P, Alonso R, Benavent J, Cruz-Sanchez F, Gich J, Pocovi M, Civeira F, Capurro S, Bachman D, Sambamurti K, Nicholas J, Pappolla MA (2010) Higher incidence of mild cognitive impairment in familial hypercholesterolemia. Am J Med 123, 267-274.
18. Bellew KM, Pigeon JG, Stang PE, Fleischman W, Gardner RM, Baker WW (2004) Hypertension and the rate of cognitive decline in patients with dementia of the Alzheimer type. Alzheimer Dis Assoc Disord 18, 208-213. (Pubitemid 40076150)
19. Goldstein FC, Ashley AV, Endeshaw YW, Hanfelt J, Lah JJ, Levey AI (2008) Effects of hypertension and hyper-cholesterolemia on cognitive functioning in patients with alzheimer disease. Alzheimer Dis Assoc Disord22, 336-342.
20. Qiu C, Winblad B, Marengoni A, Klarin I, Fastbom J, Fratiglioni L (2006) Heart failure and risk of dementia and Alzheimer disease: a population-based cohort study. Arch Intern Med 166, 1003-1008.
21. Laitinen MH, Ngandu T, Rovio S, Helkala EL, Uusitalo U, Viitanen M, Nissinen A, Tuomilehto J, Soininen H, Kivipelto M (2006) Fat intakeat midlife and risk ofdementia and Alzheimer's disease: a population-based study. Dement Geriatr Cogn Disord 22, 99-107.
22. 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. (Pubitemid 32220864)
23. Hofman A, Ott A, Breteler MM, Bots ML, Slooter AJ, van Harskamp F, van Duijn CN, Van Broeckhoven C, Grobbee DE (1997) Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study. Lancet 349, 151-154. (Pubitemid 27039193)
24. Diaz-Ruiz C, Wang J, Ksiezak-Reding H, Ho L, Qian X, Humala N, Thomas S, Martinez-Martin P, Pasinetti GM (2009) Role of hypertension in aggravating Abeta neuro-pathology of AD type and tau-mediated motor impairment. Cardiovasc Psychiatry Neurol 2009, 107-286.
25. Gentile MT, Poulet R, Di Pardo A, Cifelli G, Maffei A, Vecchione C, Passarelli F, Landolfi A, Carullo P, Lembo G (2009) Beta-amyloid deposition in brain is enhanced in mouse models of arterial hypertension. Neurobiol Aging 30, 222-228.
26. Magnoni S, Brody DL (2010) New perspectivesonamyloid-beta dynamics after acute brain injury: moving between experimental approaches and studies in the human brain. Arch Neurol 67, 1068-1073.
27. Smith DH, Chen XH, Nonaka M, Trojanowski JQ, Lee VM, Saatman KE, Leoni MJ, Xu BN, Wolf JA, Meaney DF (1999) Accumulation of amyloid beta and tau and the formation of neurofilament inclusions following diffuse brain injury in the pig. J Neuropathol Exp Neurol 58, 982-992. (Pubitemid 29441926)
28. Han F, Fukunaga K (2009) Beta-amyloid accumulation in neurovascular units following brain embolism. J Pharmacol Sci 111, 101-109.
29. Mills JD, Bailes JE, Sedney CL, Hutchins H, Sears B (2011) Omega-3 fatty acid supplementation and reduction of traumatic axonal injury in a rodent head injury model. J Neurosurg 114, 77-84.
30. Iuchi S, Weiner L (1996) Cellular and molecular physiology of Escherichia coli in the adaptation to aerobic environments. J Biochem 120, 1055-1063. (Pubitemid 27029140)
31. Bunn HF, Poyton RO (1996) Oxygen sensing and molecular adaptation to hypoxia. Physiol Rev 76, 839-885. (Pubitemid 26286080)
32. Lam TK (2010) Neuronal regulation of homeostasis by nutrient sensing. Nat Med 16, 392-395.
33. Zhang X, Zhou K, Wang R, Cui J, Lipton SA, Liao FF, Xu H, Zhang YW (2007) Hypoxia-inducible factor 1 alpha (HIF-1 alpha)-mediated hypoxia increases BACE1 expression and beta-amyloid generation. J Biol Chem 282, 10873-10880. (Pubitemid 47100783)
34. Velliquette RA, O'Connor T, Vassar R (2005) Energy inhibition elevates beta-secretase levels and activity and is potentially amyloidogenic in APP transgenic mice: possible early eventsinAlzheimer's disease pathogenesis. J Neurosci 25, 10874-10883. (Pubitemid 41692617)
35. O'Connor T, Sadleir KR, Maus E, Velliquette RA, Zhao J, Cole SL, Eimer WA, Hitt B, Bembinster LA, Lammich S, Lichtenthaler SF, Hebert SS, De Strooper B, Haass C, Bennett DA, Vassar R (2008) Phosphorylation of the translation initiation factor eIF2 alpha increases BACE1 levels and promotes amyloidogenesis. Neuron 60, 988-1009.
36. Zhang Q, Yang G, Li W, Fan Z, Sun A, Luo J, Ke ZJ (2010) Thiamine deficiency increases beta-secretase activity and accumulation of beta-amyloid peptides. Neurobiol Aging 32, 42-53.
37. Wen Y, Onyewuchi O, Yang S, Liu R, Simpkins JW (2004) Increased beta-secretase activity and expression in rats following transient cerebral ischemia. Brain Res 1009, 1-8. (Pubitemid 38553842)
38. Sun X, He G, Qing H, Zhou W, Dobie F, Cai F, Staufen-biel M, Huang LE, Song W (2006) Hypoxia facilitates Alzheimer's disease pathogenesis by up-regulating BACE1 gene expression. Proc Natl Acad Sci USA 103, 18727-18732. (Pubitemid 44913478)
39. Frederikse PH, Garland D, Zigler JS Jr, Piatigorsky J (1996) Oxidative stress increases production of beta-amyloid precursor protein and beta-amyloid (Abeta) in mammalian lenses, and Abeta has toxic effects on lens epithelial cells. J Biol Chem 271, 10169-10174. (Pubitemid 26131580)
40. Misonou H, Morishima-Kawashima M, Ihara Y (2000) Oxidative stress induces intracellular accumulation of amy-loid beta-protein (Abeta) in human neuroblastoma cells. Biochemistry 39, 6951-6959. (Pubitemid 30390389)
41. Olivieri G, Baysang G, Meier F, Muller-Spahn F, Stahe-lin HB, Brockhaus M, Brack C (2001) N-acetyl-L-cysteine protects SHSY5Y neuroblastoma cells from oxidative stress and cell cytotoxicity: effects on beta-amyloid secretion and tau phosphorylation. J Neurochem 76, 224-233. (Pubitemid 32044386)
42. Tamagno E, Parola M, Bardini P, Piccini A, Borghi R, Guglielmotto M, Santoro G, Davit A, Danni O, Smith MA, Perry G, Tabaton M (2005) Beta-site APP cleaving enzyme up-regulation induced by 4-hydroxynonenal is mediated by stress-activated protein kinases pathways. J Neurochem 92, 628-636. (Pubitemid 40189465)
43. Finocchietto P, Barreyro F, Holod S, Peralta J, Franco MC, Mendez C, Converso DP, Estevez A, Carreras MC, Poderoso JJ (2008) Control of muscle mitochondria by insulin entails activation of Akt2-mtNOS pathway: implications for the metabolic syndrome. PLoS One 3, e1749.
44. Cheng Z, Guo S, Copps K, Dong X, Kollipara R, Rodgers JT, Depinho RA, Puigserver P, White MF (2009) Foxo1 integrates insulin signaling with mitochondrial function in the liver. Nat Med 15, 1307-1311.
45. Wozniak M, Rydzewski B, Baker SP, Raizada MK (1993) The cellular and physiological actions of insulin in the central nervous system. Neurochem Int 22, 1-10.
46. Lane RF, Raines SM, Steele JW, Ehrlich ME, Lah JA, Small SA, Tanzi RE, Attie AD, Gandy S (2010) Diabetes-associated SorCS1 regulates Alzheimer's amyloid-beta metabolism: evidence for involvement of SorL1 and the retromer complex. J Neurosci 30, 13110-13115.
47. Gasparini L, Gouras GK, Wang R, Gross RS, Beal MF, Greengard P, Xu H (2001) Stimulation of beta-amyloid precursor protein trafficking by insulin reduces intraneuronal beta-amyloid and requires mitogen-activated protein kinase signaling. J Neurosci 21, 2561-2570. (Pubitemid 32298198)
48. Ho L, Qin W, Pompl PN, Xiang Z, Wang J, Zhao Z, Peng Y, Cambareri G, Rocher A, Mobbs CV, Hof PR, Pasinetti GM (2004) Diet-induced insulin resistance promotes amy-loidosisinatransgenicmouse modelofAlzheimer's disease. FASEB J 18, 902-904.
49. Wang X, Zheng W, Xie JW, Wang T, Wang SL, Teng WP, Wang ZY (2010) Insulin deficiency exacerbates cerebral amyloidosis and behavioral deficits in an Alzheimer trans-genic mouse model. Mol Neurodegener 5, 46.
50. Cao D, Lu H, Lewis TL, Li L (2007) Intake of sucrose-sweetened water induces insulin resistance and exacerbates memory deficits and amyloidosis in a transgenic mouse modelofAlzheimerdisease.J Biol Chem282, 36275-36282.
51. de la Torre JC (2006) How do heart disease and stroke become risk factors for Alzheimer's disease? Neurol Res 28, 637-644. (Pubitemid 44433323)
52. Bell RD, Zlokovic BV (2009) Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer's disease. Acta Neuropathol 118, 103-113.
53. Nagata K, Buchan RJ, Yokoyama E, Kondoh Y, Sato M, Terashi H, Satoh Y, Watahiki Y, Senova M, Hirata Y, Hatazawa J (1997) Misery perfusion with preserved vascular reactivity in Alzheimer's disease. Ann N Y Acad Sci 826, 272-281. (Pubitemid 27478049)
54. Nagata K, Sato M, Satoh Y, Watahiki Y, Kondoh Y, Sug-awara M, Box G, Wright D, Leung S, Yuya H, Shimosegawa E (2002) Hemodynamic aspects of Alzheimer's disease. Ann N Y Acad Sci 977, 391-402. (Pubitemid 35418181)
55. Nagata K, Kondoh Y, Atchison R, Sato M, Satoh Y, Watahiki Y, Hirata Y, Yokoyama E (2000) Vascular and metabolic reserve in Alzheimer's disease. Neurobiol Aging 21, 301-307. (Pubitemid 30387089)
56. Cunnane S, Nugent S, Roy M, Courchesne-Loyer A, Croteau E, Tremblay S, Castellano A, Pifferi F, Bocti C, Paquet N, Begdouri H, Bentourkia M, Turcotte E, Allard M, Barberger-Gateau P, Fulop T, Rapoport SI (2010) Brain fuel metabolism, aging, and Alzheimer's disease. Nutrition 27, 3-20.
57. Chang AM, Halter JB (2003) Aging and insulin secretion. Am J Physiol Endocrinol Metab 284, E7-E12. (Pubitemid 36076216)
58. Mangialasche F, Polidori MC, Monastero R, Ercolani S, Camarda C, Cecchetti R, Mecocci P (2009) Biomarkers of oxidative and nitrosative damage in Alzheimer's disease and mild cognitive impairment. Ageing Res Rev 8, 285-305.
59. Pratico D, Clark CM, Liun F, Rokach J, Lee VY, Tro-janowskiJQ (2002) Increase of brain oxidative stress inmild cognitive impairment: a possible predictor of Alzheimer disease. Arch Neurol 59, 972-976. (Pubitemid 34640757)
60. Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Bal-raj EK, Jones PK, Ghanbari H, Wataya T, Shimohama S, Chiba S, Atwood CS, Petersen RB, Smith MA (2001) Oxi-dative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 60, 759-767. (Pubitemid 32678256)
61. Schipper HM, Bennett DA, Liberman A, Bienias JL, Schneider JA, Kelly J, Arvanitakis Z (2006) Glial heme oxygenase-1 expression in Alzheimer disease and mild cognitive impairment. Neurobiol Aging 27, 252-261. (Pubitemid 43038549)
62. Kim D, Nguyen MD, Dobbin MM, Fischer A, Sananbe-nesi 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. (Pubitemid 47057498)
63. Shindler KS, Ventura E, Dutt M, Elliott P, Fitzgerald DC, Rostami A (2010) Oral resveratrol reduces neuronal damage in a model of multiple sclerosis. J Neuroophthalmol 30, 328-339.
64. Albani D, Polito L, Batelli S, De Mauro S, Fracasso C, Martelli G, Colombo L, Manzoni C, Salmona M, Caccia S, Negro A, Forloni G (2009) The SIRT1 activator resveratrol protects SK-N-BE cells from oxidative stress and against toxicity caused by alpha-synuclein or amyloid-beta (1-42) peptide. J Neurochem 110, 1445-1456.
65. Guarente L (2000) Sir2 links chromatin silencing, metabolism, and aging. Genes Dev 14, 1021-1026. (Pubitemid 30324417)
66. Tissenbaum HA, Guarente L (2001) Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410, 227-230. (Pubitemid 32216597)
67. Rogina B, Helfand SL (2004) Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci USA 101, 15998-16003. (Pubitemid 39507916)
68. Lim JH, Lee YM, Chun YS, Chen J, Kim JE, Park JW (2010) Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1 alpha. Mol Cell 38, 864-878.
69. Yu J, Auwerx J (2009) The role of sirtuins in the control of metabolic homeostasis. Ann N Y Acad Sci 1173 (Suppl 1), E10-E19.
70. Oberdoerffer P, Michan S, McVay M, Mostoslavsky R, Vann J, Park SK, Hartlerode A, Stegmuller J, Hafner A, Loerch P, Wright SM, Mills KD, Bonni A, Yankner BA, Scully R, Prolla TA, Alt FW, Sinclair DA (2008) SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging. Cell 135, 907-918.
71. Gillum MP, Erion DM, Shulman GI (2011) Sirtuin-1 regulation of mammalian metabolism. Trends Mol Med 17, 8-13.
72. Donmez G, Wang D, Cohen DE, Guarente L (2010) SIRT1 suppresses beta-amyloid production by activating the alpha-secretase gene ADAM10. Cell 142, 320-332.
73. Wu A, Ying Z, Gomez-Pinilla F (2006) Oxidative stress modulates Sir2 alpha in rat hippocampus and cerebral cortex. Eur J Neurosci 23, 2573-2580. (Pubitemid 43801449)
74. Julien C, Tremblay C, Emond V, Lebbadi M, Salem N Jr, Bennett DA, Calon F (2009) Sirtuin 1 reduction parallels the accumulation of tau in Alzheimer disease. J Neuropathol Exp Neurol 68, 48-58.
75. Webster NJ, Green KN, Settle VJ, Peers C, Vaughan PF (2004) Altered processing of the amyloid precursor protein and decreased expression of ADAM 10 by chronic hypoxia in SH-SY5Y: no role for the stress-activated JNK and p38 signalling pathways. Brain Res Mol Brain Res 130, 161-169. (Pubitemid 39440746)
76. Giuffrida ML, Caraci F, Pignataro B, Cataldo S, De Bona P, Bruno V, Molinaro G, Pappalardo G, Messina A, Palmigiano A, Garozzo D, Nicoletti F, Rizzarelli E, Copani A (2009) Beta-amyloid monomers are neuroprotective. J Neurosci 29, 10582-10587.
77. Yankner BA, Duffy LK, Kirschner DA (1990) Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides. Science 250, 279-282.
78. Hayashi T, Shishido N, Nakayama K, Nunomura A, Smith MA, Perry G, Nakamura M (2007) Lipid peroxidation and 4-hydroxy-2-nonenal formation by copper ion bound to amyloid-beta peptide. Free Radic Biol Med 43, 1552-1559. (Pubitemid 47615399)
79. Kontush A, Berndt C, Weber W, Akopyan V, Arlt S, Schip-pling S, Beisiegel U (2001) Amyloid-beta is an antioxidant for lipoproteins in cerebrospinal fluid and plasma. Free Radic Biol Med 30, 119-128. (Pubitemid 32008095)
80. Soucek T, Cumming R, Dargusch R, Maher P, Schubert D (2003) The regulation of glucose metabolism by HIF-1 mediates a neuroprotective response to amyloid beta pep-tide. Neuron 39, 43-56. (Pubitemid 36830947)
81. Duce JA, Tsatsanis A, Cater MA, James SA, Robb E, Wikhe K, Leong SL, Perez K, Johanssen T, Greenough MA, Cho HH, Galatis D, Moir RD, Masters CL, McLean C, Tanzi RE, Cappai R, Barnham KJ, Ciccotosto GD, Rogers JT, Bush AI (2010) Iron-export ferroxidase activity of beta-amyloid precursor protein isinhibited byzincinAlzheimer's disease. Cell 142, 857-867.
82. 2+ channels in central neurones. Neurobiol Aging 27, 439-445. (Pubitemid 43185329)
83. Lublin AL, Gandy S (2010) Amyloid-beta oligomers: possible roles as key neurotoxins in Alzheimer's disease. Mt Sinai J Med 77, 43-49.
84. Zhu X, Lee HG, Perry G, Smith MA (2007) Alzheimer disease, the two-hit hypothesis: an update. Biochim Biophys Acta 1772, 494-502. (Pubitemid 46400383)
85. Poon HF, Joshi G, Sultana R, Farr SA, Banks WA, Morley JE, Calabrese V, Butterfield DA (2004) Antisense directed at the Abeta region of APP decreases brain oxidative markers in aged senescence accelerated mice. Brain Res 1018, 86-96. (Pubitemid 38942865)
86. Kumar VB, Farr SA, Flood JF, Kamlesh V, Franko M, Banks WA, Morley JE (2000) Site-directed antisense oligonu-cleotide decreases the expression of amyloid precursor protein and reverses deficits in learning and memory in aged SAMP8 mice. Peptides 21, 1769-1775. (Pubitemid 32058851)
87. Bucciantini M, Giannoni E, Chiti F, Baroni F, Formigli L, Zurdo J, Taddei N, Ramponi G, Dobson CM, Stefani M (2002) Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases. Nature 416, 507-511. (Pubitemid 34288846)
88. Bishop NA, Lu T, Yankner BA (2010) Neural mechanisms of ageing and cognitive decline. Nature 464, 529-535.
89. Golde TE, Petrucelli L, Lewis J (2010) Targeting Abeta and tau in Alzheimer's disease, an early interim report. Exp Neurol 223, 252-266.
90. Whitehouse P, George, DR (2008) The Myth of Alzheimer's: What You Aren't Being Told About Today's Most Dreaded Diagnosis, St. Martin's Press, New York.
91. O'Connor S, Prusiner S, Dychtwald K (2010) The Age of Alzheimer's. The New York Times 27 October. Accessed 23-3-11 at http://www.nytimes.com/2010/10/ 28/opinion/28oconnor.html
92. George DR (2010) Overcoming the social death of dementia through language. The Lancet 376, 586-587.
93. Petrosini L, De Bartolo P, Foti F, Gelfo F, Cutuli D, Leggio MG, Mandolesi L (2009) On whether the environmental enrichment may provide cognitive and brain reserves. Brain Res Rev 61, 221-239.
94. Stein J, Greater Boston Physicians for Social R, Science, Environmental Health N (2008) Environmental Threats to Healthy Aging: with a Closer Look at Alzheimer's & Parkinson's Diseases, Greater Boston Physicians for Social Responsibilty: Science and Environmental Health Network, Boston.
95. Perneczky R, Wagenpfeil S, Lunetta KL, Cupples LA, Green RC, Decarli C, Farrer LA, Kurz A (2010) Head circumference, atrophy, and cognition: implications for brain reserve in Alzheimer disease. Neurology 75, 137-142.
96. Mortimer JA, Snowdon DA, Markesbery WR (2003) Head circumference, education and risk of dementia: findings from the Nun Study. J Clin Exp Neuropsychol 25, 671-679. (Pubitemid 36808152)
97. McDowell I, Xi G, Lindsay J, Tierney M (2007) Mapping the connections between education and dementia. J Clin Exp Neuropsychol 29, 127-141.
98. Garibotto V, Borroni B, Kalbe E, Herholz K, Salmon E, Holtoff V, Sorbi S, Cappa SF, Padovani A, Fazio F, Perani D (2008) Education and occupation as proxies for reserve in aMCI converters and AD: FDG-PET evidence. Neurology 71, 1342-1349.
99. Letenneur L, Gilleron V, Commenges D, Helmer C, Orgogozo JM, Dartigues JF (1999) Are sex and educational level independent predictors of dementia and Alzheimer's disease? Incidence data from the PAQUID project. J Neurol Neurosurg Psychiatry 66, 177-183. (Pubitemid 29103518)
100. Kemppainen NM, Aalto S, Karrasch M, Nagren K, Savisto N, Oikonen V, Viitanen M, Parkkola R, Rinne JO (2008) Cognitive reserve hypothesis: Pittsburgh Compound B and fluorodeoxyglucose positron emission tomography in relation to education in mild Alzheimer's disease. Ann Neurol 63, 112-118. (Pubitemid 351240557)
101. Richards M, Wadsworth ME (2004) Long term effects of early adversity on cognitive function. Arch Dis Child 89, 922-927.
102. Scarmeas N, Stern Y (2003) Cognitive reserve and lifestyle. J Clin Exp Neuropsychol 25, 625-633. (Pubitemid 36808148)
103. Kramer AF, Hahn S, Cohen NJ, Banich MT, McAuley E, Harrison CR, Chason J, Vakil E, Bardell L, Boileau RA, Colcombe A (1999) Ageing, fitness and neurocognitive function. Nature 400, 418-419.
104. Richards M, Sacker A (2003) Lifetime antecedents of cognitive reserve. J Clin Exp Neuropsychol 25, 614-624. (Pubitemid 36808147)
105. Richards M, Hardy R, Wadsworth ME (2003) Does active leisure protect cognition? Evidence from a national birth cohort. Soc Sci Med 56, 785-792. (Pubitemid 36135809)
106. Staff RT, Murray AD, Deary IJ, Whalley LJ (2004) What provides cerebral reserve? Brain 127, 1191-1199. (Pubitemid 38623052)
107. Akbaraly TN, Portet F, Fustinoni S, Dartigues JF, Artero S, Rouaud O, Touchon J, Ritchie K, Berr C (2009) Leisure activities and the risk ofdementia inthe elderly: results from the Three-City Study. Neurology 73, 854-861.
108. Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A, Plymate SR, Fishel MA, Watson GS, Cholerton BA, Duncan GE, Mehta PD, Craft S (2010) Effects of aerobic exercise on mild cognitive impairment: a controlled trial. Arch Neurol 67, 71-79.
109. Jankowsky JL, Melnikova T, Fadale DJ, Xu GM, Slunt HH, Gonzales V, Younkin LH, Younkin SG, Borchelt DR, Savonenko AV (2005) Environmental enrichment mitigates cognitive deficits in a mouse model of Alzheimer's disease. J Neurosci 25, 5217-5224. (Pubitemid 40726973)
110. Costa DA, Cracchiolo JR, Bachstetter AD, Hughes TF, Bales KR, Paul SM, Mervis RF, Arendash GW, Potter H (2007) Enrichment improves cognition in AD mice by amyloid-related and unrelated mechanisms. Neurobiol Aging 28, 831-844. (Pubitemid 46613825)
111. Berardi N, Braschi C, Capsoni S, Cattaneo A, Maffei L (2007) Environmental enrichment delays the onset of memory deficits and reduces neuropathological hallmarks in a mouse model of Alzheimer-like neurodegeneration. J Alz-heimers Dis 11, 359-370. (Pubitemid 47094033)
112. Herring A, Ambree O, Tomm M, Habermann H, Sachser N, Paulus W, Keyvani K (2009) Environmental enrichment enhances cellular plasticity in transgenic mice with Alzheimer-like pathology. Exp Neurol 216, 184-192.
113. Hu YS, Xu P, Pigino G, Brady ST, Larson J, Lazarov O (2010) Complex environment experience rescues impaired neurogenesis, enhances synaptic plasticity, and attenuates neuropathology in familial Alzheimer's disease-linked APPswe/PS1DeltaE9 mice. FASEB J 24, 1667-1681.
114. Zhao C, Deng W, Gage FH (2008) Mechanisms and functional implicationsofadult neurogenesis.Cell132, 645-660.
115. Fabel K, Wolf SA, Ehninger D, Babu H, Leal-Galicia P, Kempermann G (2009) Additive effects of physical exercise and environmental enrichment on adult hippocampal neurogenesis in mice. Front Neurosci 3, 50.
116. de la Fuente-Fernandez R (2006) Impact of neuroprotection on incidence of Alzheimer's disease. PLoS One 1, e52.