Cholesterol and synaptic compensatory mechanisms in Alzheimer's disease mice brain during aging

Journal of Alzheimer's Disease

Volumn 31, Issue 4, 2012, Pages 813-826

  Jansen, Diane ^a   Janssen, Carola I F ^a   Vanmierlo, Tim ^b   Dederen, Pieter J ^a   Van Rooij, Daan ^a   Zinnhardt, Bastian ^a   Nobelen, Cindy L M ^a   Janssen, Anna Lena ^a   Hafkemeijer, Anne ^a   Mutsaers, Martina P C ^a   Doedée, Anne M C M ^a   Kuipers, Almar A M ^c   Broersen, Laus M ^c   Mulder, Monique ^d   Kiliaan, Amanda J ^a  

^a RADBOUD UNIVERSITY   (Netherlands)

^b MAASTRICHT UNIVERSITY   (Netherlands)

^c DANONE RESEARCH   (Netherlands)

^d ERASMUS MEDICAL CENTER   (Netherlands)

Author keywords

Aging; Alzheimer's disease; amyloid ; cholesterol; glucose transporter type 1; hippocampus; liver X receptor; synapse; synaptophysin; T0901317; transgenic mice

Indexed keywords

AMYLOID BETA PROTEIN; CHOLESTEROL; GLUCOSE TRANSPORTER 1; N (2,2,2 TRIFLUOROETHYL) N [4 [2,2,2 TRIFLUORO 1 HYDROXY 1 (TRIFLUOROMETHOXY)ETHYL]PHENYL]BENZENESULFONAMIDE; SYNAPTOPHYSIN;

AGING; ALZHEIMER DISEASE; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN BLOOD FLOW; BRAIN ISCHEMIA; CAPILLARY DENSITY; CHOLESTEROL DIET; DOSE RESPONSE; DRUG EFFECT; HIPPOCAMPUS; IMMUNOHISTOCHEMISTRY; MOUSE; NERVE DEGENERATION; NEUROPROTECTION; NONHUMAN; PRESYNAPTIC MEMBRANE; PRIORITY JOURNAL; SUBCORTEX; SYNAPSE; TREATMENT DURATION;

EID: 84866341940     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-2012-120298     Document Type: Article

References (108)

1. Mattson MP (2004) Pathways towards and away from Alzheimer's disease. Nature 430, 631-639.
2. Selkoe DJ, SchenkD(2003) Alzheimer's disease: Molecular understanding predicts amyloid-based therapeutics. Annu Rev Pharmacol Toxicol 43, 545-584.
3. de la Torre JC (2004) Is Alzheimer's disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics. Lancet Neurol 3, 184-190.
4. Bishop GM, Robinson SR (2002) The amyloid hypothesis: Let sleeping dogmas lie? Neurobiol Aging 23, 1101-1105.
5. Davis DG, Schmitt FA, Wekstein DR, Markesbery WR (1999) Alzheimer neuropathologic alterations in aged cognitively normal subjects. J Neuropathol Exp Neurol 58, 376-388.
6. Fernando MS, Ince PG (2004) Vascular pathologies and cognition in a population-based cohort of elderly people. J Neurol Sci 226, 13-17.
7. Mintun MA, Larossa GN, Sheline YI, Dence CS, Lee SY, Mach RH, Klunk WE, Mathis CA, DeKosky ST, Morris JC (2006) PIB in a nondemented population: Potential antecedent marker of Alzheimer disease. Neurology 67, 446- 452.
8. 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.
9. Larson ME, Lesne SE (2012) Soluble Abeta oligomer production and toxicity. J Neurochem 120(Suppl 1), 125-139.
10. Walsh DM, Selkoe DJ (2007) A beta oligomers - a decade of discovery. J Neurochem 101, 1172-1184.
11. Skoog I, Gustafson D (2002) Hypertension and related factors in the etiology of Alzheimer's disease. Ann N Y Acad Sci 977, 29-36.
12. Breteler MM (2000) Vascular risk factors for Alzheimer's disease: An epidemiologic perspective. Neurobiol Aging 21, 153-160.
13. Breteler MM (2000) Vascular involvement in cognitive decline and dementia. Epidemiologic evidence from the Rotterdam Study and the Rotterdam Scan Study. Ann N Y Acad Sci 903, 457-465.
14. Meyer JS, Terayama Y, Konno S, Akiyama H, Margishvili GM, Mortel KF (1998) Risk factors for cerebral degenerative changes and dementia. Eur Neurol 39(Suppl 1), 7-16.
15. Kalmijn S, Feskens EJ, Launer LJ, Kromhout D (1997) Polyunsaturated fatty acids, antioxidants, and cognitive function in very old men. Am J Epidemiol 145, 33-41.
16. Kalmijn S, Launer LJ, Ott A, Witteman JC, Hofman A, Breteler MM (1997) Dietary fat intake and the risk of incident dementia in the Rotterdam Study. Ann Neurol 42, 776-782.
17. Dosunmu R, Wu J, Basha MR, Zawia NH (2007) Environmental and dietary risk factors in Alzheimer's disease. Expert Rev Neurother 7, 887-900.
18. Kivipelto M, Helkala EL, Laakso MP, Hanninen T, Hallikainen M, Alhainen K, Soininen H, Tuomilehto J, Nissinen A (2001) Midlife vascular risk factors and Alzheimer's disease in later life: Longitudinal, population based study. BMJ 322, 1447-1451.
19. Kivipelto M, Helkala EL, Laakso MP, Hanninen T, Hallikainen M, Alhainen K, Iivonen S, Mannermaa A, Tuomilehto J, Nissinen A, Soininen H (2002) ApolipoproteinEepsilon4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease. Ann Intern Med 137, 149-155.
20. Kivipelto M, Ngandu T, Fratiglioni L, Viitanen M, Kareholt I,Winblad B, Helkala EL, Tuomilehto J, Soininen H, NissinenA (2005) Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch Neurol 62, 1556-1560.
21. Casserly I, Topol E (2004) Convergence of atherosclerosis and Alzheimer's disease: Inflammation, cholesterol, and misfolded proteins. Lancet 363, 1139-1146.
22. Canevari L, Clark JB (2007) Alzheimer's disease and cholesterol: The fat connection. Neurochem Res 32, 739-750.
23. Refolo LM, Malester B, LaFrancois J, Bryant-Thomas T, Wang R, Tint GS, Sambamurti K, Duff K, Pappolla MA (2000) Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model. Neurobiol Dis 7, 321-331.
24. Hooijmans CR, Graven C, Dederen PJ, Tanila H, van Groen T, Kiliaan AJ (2007) Amyloid beta deposition is related to decreased glucose transporter-1 levels and hippocampal atrophy in brains of aged APP/PS1 mice. Brain Res 1181, 93-103.
25. Oksman M, Iivonen H, Hogyes E, Amtul Z, Penke B, Leenders I, Broersen L, Lutjohann D, Hartmann T, Tanila H (2006) Impact of different saturated fatty acid, polyunsaturated fatty acid and cholesterol containing diets on beta-amyloid accumulation in APP/PS1 transgenic mice. Neurobiol Dis 23, 563-572.
26. Shie FS, Jin LW, Cook DG, Leverenz JB, LeBoeuf RC (2002) Diet-induced hypercholesterolemia enhances brain A beta accumulation in transgenic mice. Neuroreport 13, 455-459.
27. Refolo LM, Pappolla MA, LaFrancois J, Malester B, Schmidt SD, Thomas-Bryant T, Tint GS,Wang R, Mercken M, Petanceska SS, Duff KE (2001) A cholesterol-lowering drug reduces beta-amyloid pathology in a transgenic mouse model of Alzheimer's disease. Neurobiol Dis 8, 890-899.
28. Simons M,Keller P, De Strooper B, Beyreuther K, Dotti CG, Simons K (1998) Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons. Proc Natl Acad Sci U S A 95, 6460-6464.
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 U S A 98, 5856-5861.
30. Wang L, Schuster GU, Hultenby K, Zhang Q, Andersson S, Gustafsson JA (2002) Liver X receptors in the central nervous system: From lipid homeostasis to neuronal degeneration. Proc Natl Acad Sci U S A 99, 13878-13883.
31. EckertGP,Vardanian L, RebeckGW, BurnsMP(2007) Regulation of central nervous system cholesterol homeostasis by the liver X receptor agonist TO-901317. Neurosci Lett 423, 47-52.
32. Hooijmans CR, Kiliaan AJ (2008) Fatty acids, lipid metabolism and Alzheimer pathology. Eur J Pharmacol 585, 176-196.
33. Kim J, Basak JM, Holtzman DM (2009) The role of apolipoprotein E in Alzheimer's disease. Neuron 63, 287-303.
34. Hirsch-Reinshagen V, Burgess BL, Wellington CL (2009) Why lipids are important for Alzheimer disease? Mol Cell Biochem 326, 121-129.
35. Schultz JR, Tu H, Luk A, Repa JJ, Medina JC, Li L, Schwendner S,Wang S, Thoolen M, Mangelsdorf DJ, Lustig KD, Shan B (2000) Role of LXRs in control of lipogenesis. Genes Dev 14, 2831-2838.
36. Wojcicka G, Jamroz-Wisniewska A, Horoszewicz K, Beltowski J (2007) Liver X receptors (LXRs). Part I: Structure, function, regulation of activity, and role in lipid metabolism. Postepy Hig Med Dosw (Online) 61, 736-759.
37. Koldamova RP, Lefterov IM, Ikonomovic MD, Skoko J, Lefterov PI, Isanski BA, DeKosky ST, Lazo JS (2003) 22R-hydroxycholesterol and 9-cis-retinoic acid induce ATP-binding cassette transporter A1 expression and cholesterol efflux in brain cells and decrease amyloid beta secretion. J Biol Chem 278, 13244- 13256.
38. Koldamova RP, Lefterov IM, Staufenbiel M, Wolfe D, Huang S, Glorioso JC,Walter M, Roth MG, Lazo JS (2005) The liver X receptor ligand T0901317 decreases amyloid beta production in vitro and in a mouse model of Alzheimer's disease. J Biol Chem 280, 4079-4088.
39. SunY,Yao J, KimTW, Tall AR (2003) Expression of liverX receptor target genes decreases cellular amyloid beta peptide secretion. J Biol Chem 278, 27688-27694.
40. Riddell DR, Zhou H, Comery TA,Kouranova E, Lo CF,Warwick HK, Ring RH, Kirksey Y, Aschmies S, Xu J, Kubek K, HirstWD,Gonzales C, ChenY, Murphy E, Leonard S,Vasylyev D, Oganesian A, Martone RL, Pangalos MN, Reinhart PH, Jacobsen JS (2007) The LXR agonist TO901317 selectively lowers hippocampal Abeta42 and improves memory in the Tg2576 mouse model of Alzheimer's disease. Mol Cell Neurosci 34, 621-628.
41. Vanmierlo T, Rutten K, Dederen J, BloksVW, van Vark-van der Zee LC, Kuipers F, Kiliaan A, Blokland A, Sijbrands EJ, Steinbusch H, Prickaerts J, Lutjohann D, Mulder M (2011) Liver X receptor activation restores memory in aged AD mice without reducing amyloid. Neurobiol Aging 32, 1262-1272.
42. Dietschy JM, Turley SD (2001) Cholesterol metabolism in the brain. Curr Opin Lipidol 12, 105-112.
43. Lutjohann D (2006) Cholesterol metabolism in the brain: Importance of 24S-hydroxylation. Acta Neurol Scand Suppl 185, 33-42.
44. Bjorkhem I (2006) Crossing the barrier: Oxysterols as cholesterol transporters and metabolic modulators in the brain. J Intern Med 260, 493-508.
45. Hooijmans CR, Van der Zee CE, Dederen PJ, Brouwer KM, Reijmer YD, van Groen T, Broersen LM, Lutjohann D, Heerschap A, Kiliaan AJ (2009) DHA and cholesterol containing diets influence Alzheimer-like pathology, cognition and cerebral vasculature in APPswe/PS1dE9 mice. Neurobiol Dis 33, 482-498.
46. Skoog I, Gustafson D (2006) Update on hypertension and Alzheimer's disease. Neurol Res 28, 605-611.
47. Skoog I, Gustafson D (2003) Hypertension, hypertensionclustering factors and Alzheimer's disease. Neurol Res 25, 675-680.
48. Hooijmans CR, Rutters F, Dederen PJ, Gambarota G,Veltien A, van Groen T, Broersen LM, Lutjohann D, Heerschap A, Tanila H, Kiliaan AJ (2007) Changes in cerebral blood volume and amyloid pathology in aged Alzheimer APP/PS1 mice on a docosahexaenoic acid (DHA) diet or cholesterol enriched Typical Western Diet (TWD). Neurobiol Dis 28, 16-29.
49. Harris GJ, Lewis RF, Satlin A, English CD, Scott TM, Yurgelun-Todd DA, Renshaw PF (1998) Dynamic susceptibility contrast MR imaging of regional cerebral blood volume in Alzheimer disease: A promising alternative to nuclear medicine. AJNR Am J Neuroradiol 19, 1727-1732.
50. Tohgi H, Yonezawa H, Takahashi S, Sato N, Kato E, Kudo M, Hatano K, Sasaki T (1998) Cerebral blood flow and oxygen metabolism in senile dementia of Alzheimer's type and vascular dementia with deep white matter changes. Neuroradiology 40, 131-137.
51. Jankowsky JL, Slunt HH, Ratovitski T, Jenkins NA, Copeland NG, Borchelt DR (2001) Co-expression of multiple transgenes in mouse CNS: A comparison of strategies. Biomol Eng 17, 157-165.
52. Jankowsky JL, Fadale DJ, Anderson J, Xu GM, Gonzales V, Jenkins NA, Copeland NG, Lee MK, Younkin LH, Wagner SL, Younkin SG, Borchelt DR (2004) Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: Evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet 13, 159-170.
53. Choeiri C, StainesW, Messier C (2002) Immunohistochemical localization and quantification of glucose transporters in the mouse brain. Neuroscience 111, 19-34.
54. Vannucci SJ, Maher F, Simpson IA (1997) Glucose transporter proteins in brain: Delivery of glucose to neurons and glia. Glia 21, 2-21.
55. Maher F, Vannucci SJ, Simpson IA (1994) Glucose transporter proteins in brain. FASEB J 8, 1003-1011.
56. Kalaria RN, Harik SI (1989) Reduced glucose transporter at the blood-brain barrier and in cerebral cortex in Alzheimer disease. J Neurochem 53, 1083-1088.
57. Horwood N, Davies DC (1994) Immunolabelling of hippocampal microvessel glucose transporter protein is reduced in Alzheimer's disease. Virchows Arch 425, 69-72.
58. Simpson IA, Chundu KR, Davies-Hill T, Honer WG, Davies P (1994) Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer's disease. Ann Neurol 35, 546-551.
59. Kouznetsova E, Klingner M, Sorger D, Sabri O, Grossmann U, Steinbach J, Scheunemann M, Schliebs R (2006) Developmental and amyloid plaque-related changes in cerebral cortical capillaries in transgenic Tg2576 Alzheimer mice. Int J Dev Neurosci 24, 187-193.
60. Jahn R, Sudhof TC (1993) Synaptic vesicle traffic: Rush hour in the nerve terminal. J Neurochem 61, 12-21.
61. Irizarry MC, Soriano F, McNamara M, Page KJ, Schenk D, Games D, Hyman BT (1997) Abeta deposition is associated with neuropil changes, but not with overt neuronal loss in the human amyloid precursor protein V717F (PDAPP) transgenic mouse. J Neurosci 17, 7053-7059.
62. Shukla C, Bridges LR (1999) Regional distribution of tau, beta-amyloid and beta-amyloid precursor protein in the Alzheimer's brain: A quantitative immunolabelling study. Neuroreport 10, 3785-3789.
63. Franklin KBJ, Paxinos G (1997) The mouse brain in stereotaxic coordinates. Academic Press, San Diego.
64. Mulder M, Koopmans G, Wassink G, Al Mansouri G, Simard ML, Havekes LM, Prickaerts J, Blokland A (2007) LDL receptor deficiency results in decreased cell proliferation and presynaptic bouton density in the murine hippocampus. Neurosci Res 59, 251-256.
65. Rutten BP, Van der Kolk NM, Schafer S, van Zandvoort MA, Bayer TA, Steinbusch HW, Schmitz C (2005) Agerelated loss of synaptophysin immunoreactive presynaptic boutons within the hippocampus of APP751SL, PS1M146L, and APP751SL/PS1M146L transgenic mice. Am J Pathol 167, 161-173.
66. DeKosky ST, Scheff SW, Styren SD (1996) Structural correlates of cognition in dementia: Quantification and assessment of synapse change. Neurodegeneration 5, 417- 421.
67. Selkoe DJ (2002) Alzheimer's disease is a synaptic failure. Science 298, 789-791.
68. Scheff SW, Price DA (2003) Synaptic pathology in Alzheimer's disease: A review of ultrastructural studies. Neurobiol Aging 24, 1029-1046.
69. Scheff SW, Price DA, Schmitt FA, Mufson EJ (2006) Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment. Neurobiol Aging 27, 1372-1384.
70. DeKosky ST, Scheff SW (1990) Synapse loss in frontal cortex biopsies in Alzheimer's disease: Correlation with cognitive severity. Ann Neurol 27, 457-464.
71. Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R (1991) Physical basis of cognitive alterations in Alzheimer's disease: Synapse loss is the major correlate of cognitive impairment. Ann Neurol 30, 572-580.
72. Hamos JE, DeGennaro LJ, Drachman DA (1989) Synaptic loss in Alzheimer's disease and other dementias. Neurology 39, 355-361.
73. Scheff SW, Sparks DL, PriceDA(1996) Quantitative assessment of synaptic density in the outer molecular layer of the hippocampal dentate gyrus in Alzheimer's disease. Dementia 7, 226-232.
74. Scheff SW, Price DA (1998) Synaptic density in the inner molecular layer of the hippocampal dentate gyrus in Alzheimer disease. J Neuropathol Exp Neurol 57, 1146- 1153.
75. Leuba G, Savioz A, Vernay A, Carnal B, Kraftsik R, Tardif E, Riederer I, Riederer BM (2008) Differential changes in synaptic proteins in the Alzheimer frontal cortex with marked increase in PSD-95 postsynaptic protein. J Alzheimers Dis 15, 139-151.
76. 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 abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: Synaptotoxicity without plaque formation. J Neurosci 20, 4050-4058.
77. Masliah E, Sisk A, Mallory M, Mucke L, Schenk D, Games D (1996) Comparison of neurodegenerative pathology in transgenic mice overexpressing V717F beta-amyloid precursor protein and Alzheimer's disease. J Neurosci 16, 5795-5811.
78. Dong H, Martin MV, Chambers S, Csernansky JG (2007) Spatial relationship between synapse loss and beta-amyloid deposition in Tg2576 mice. J Comp Neurol 500, 311-321.
79. Yao PJ, Bushlin I, Furukawa K (2005) Preserved synaptic vesicle recycling in hippocampal neurons in a mouse Alzheimer's disease model. Biochem Biophys Res Commun 330, 34-38.
80. King DL, Arendash GW (2002) Maintained synaptophysin immunoreactivity in Tg2576 transgenic mice during aging: Correlations with cognitive impairment. Brain Res 926, 58-68.
81. Boncristiano S, Calhoun ME, HowardV, Bondolfi L, Kaeser SA,Wiederhold KH, Staufenbiel M, Jucker M (2005) Neocortical synaptic bouton number is maintained despite robust amyloid deposition in APP23 transgenic mice. Neurobiol Aging 26, 607-613.
82. Mukaetova-Ladinska EB, Garcia-Siera F, Hurt J, Gertz HJ, Xuereb JH, Hills R, Brayne C, Huppert FA, Paykel ES, McGee M, Jakes R, Honer WG, Harrington CR, Wischik CM (2000) Staging of cytoskeletal and beta-amyloid changes in human isocortex reveals biphasic synaptic protein response during progression of Alzheimer's disease.Am J Pathol 157, 623-636.
83. Masliah E, Mallory M, Hansen L, DeTeresa R, Alford M, Terry R (1994) Synaptic and neuritic alterations during the progression of Alzheimer's disease. Neurosci Lett 174, 67- 72.
84. Bronfman FC, Moechars D, Van Leuven F (2000) Acetylcholinesterase- positive fiber deafferentation and cell shrinkage in the septohippocampal pathway of aged amyloid precursor protein london mutant transgenic mice. Neurobiol Dis 7, 152-168.
85. Masliah E, Crews L, Hansen L (2006) Synaptic remodeling during aging and in Alzheimer's disease. J Alzheimers Dis 9, 91-99.
86. Arendt T (2001) Alzheimer's disease as a disorder of mechanisms underlying structural brain self-organization. Neuroscience 102, 723-765.
87. Lue LF, Kuo YM, Roher AE, Brachova L, Shen Y, Sue L, Beach T,Kurth JH, Rydel RE, Rogers J (1999) Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer's disease. Am J Pathol 155, 853-862.
88. Cummings BJ, Pike CJ, Shankle R, Cotman CW (1996) Beta-amyloid deposition and other measures of neuropathology predict cognitive status in Alzheimer's disease. Neurobiol Aging 17, 921-933.
89. Terry RD (1996) The pathogenesis of Alzheimer disease: An alternative to the amyloid hypothesis. J Neuropathol Exp Neurol 55, 1023-1025.
90. Bartoo GT, Nochlin D, Chang D, Kim Y, Sumi SM (1997) The mean A beta load in the hippocampus correlates with duration and severity of dementia in subgroups of Alzheimer disease. J Neuropathol Exp Neurol 56, 531-540.
91. 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.
92. McLean CA, Cherny RA, Fraser FW, Fuller SJ, Smith MJ, Beyreuther K, Bush AI, Masters CL (1999) Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease. Ann Neurol 46, 860-866.
93. LambertMP, BarlowAK, Chromy BA, Edwards C, Freed R, Liosatos M, Morgan TE, Rozovsky I, Trommer B,Viola KL, Wals P, Zhang C, Finch CE, Krafft GA, Klein WL (1998) Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. Proc Natl Acad Sci U S A 95, 6448-6453.
94. Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, Rowan MJ, Selkoe DJ (2002) Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416, 535-539.
95. Cleary JP, Walsh DM, Hofmeister JJ, Shankar GM, Kuskowski MA, Selkoe DJ, Ashe KH (2005) Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function. Nat Neurosci 8, 79-84.
96. Lesne S, Koh MT, Kotilinek L, Kayed R, Glabe CG, Yang A, Gallagher M, Ashe KH (2006) A specific amyloid-beta protein assembly in the brain impairs memory. Nature 440, 352-357.
97. Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, Brett FM, Farrell MA, Rowan MJ, Lemere CA, Regan CM,Walsh DM, Sabatini BL, Selkoe DJ (2008) Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat Med 14, 837-842.
98. Lacor PN, Buniel MC, Furlow PW, Clemente AS, Velasco PT, Wood M, Viola KL, Klein WL (2007) Abeta oligomerinduced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer's disease. J Neurosci 27, 796-807.
99. Garcia-Alloza M, Robbins EM, Zhang-Nunes SX, Purcell SM, Betensky RA, Raju S, Prada C, Greenberg SM, Bacskai BJ, Frosch MP (2006) Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease. Neurobiol Dis 24, 516-524.
100. Mauch DH, Nagler K, Schumacher S, Goritz C, Muller EC, Otto A, Pfrieger FW (2001) CNS synaptogenesis promoted by glia-derived cholesterol. Science 294, 1354-1357.
101. Pfrieger FW (2003) Cholesterol homeostasis and function in neurons of the central nervous system. Cell Mol Life Sci 60, 1158-1171.
102. Thiele C, Hannah MJ, Fahrenholz F, Huttner WB (2000) Cholesterol binds to synaptophysin and is required for biogenesis of synaptic vesicles. Nat Cell Biol 2, 42-49.
103. Mitter D, Reisinger C, Hinz B, Hollmann S, Yelamanchili SV, Treiber-Held S, Ohm TG, Herrmann A, Ahnert-Hilger G (2003) The synaptophysin/synaptobrevin interaction critically depends on the cholesterol content. J Neurochem 84, 35-42.
104. Calon F, Cole G (2007) Neuroprotective action of omega-3 polyunsaturated fatty acids against neurodegenerative diseases: Evidence from animal studies. Prostaglandins Leukot Essent Fatty Acids 77, 287-293.
105. Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Aggarwal N, Schneider J, Wilson RS (2003) Dietary fats and the risk of incident Alzheimer disease. Arch Neurol 60, 194-200.
106. Calon F, Lim GP, Morihara T, Yang F, Ubeda O, Salem N Jr, Frautschy SA, Cole GM (2005) Dietary n-3 polyunsaturated fatty acid depletion activates caspases and decreases NMDA receptors in the brain of a transgenic mouse model of Alzheimer's disease. Eur J Neurosci 22, 617-626.
107. Julien C, Tremblay C, Phivilay A, Berthiaume L, Emond V, Julien P, Calon F (2010) High-fat diet aggravates amyloidbeta and tau pathologies in the 3×Tg-AD mouse model. Neurobiol Aging 31, 1516-1531.
108. Boxerman JL, Hamberg LM, Rosen BR, Weisskoff RM (1995) MR contrast due to intravascular magnetic susceptibility perturbations. Magn Reson Med 34, 555-566.