Cholesterol and Alzheimer's disease—is there a relation?

Mechanisms of Ageing and Development - Tập 127 - Trang 138-147 - 2006
Magnus Sjögren1, Michelle Mielke2, Deborah Gustafson3, Peter Zandi4, Ingmar Skoog3
1Department of Experimental Geriatrics, Neurotec, Karolinska Institute, Huddinge, Sweden
2Center on Aging and Health and The Alzheimer Disease Research Center, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
3Institute of Clinical Neuroscience, Göteborg University, Göteborg, Sweden
4Department of Mental Health, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA

Tài liệu tham khảo

Alaupovic, 1982, The role of apolipoproteins in lipid transport processes, Ric. Clin. Lab., 12, 3, 10.1007/BF02909305 Aronson, 1990, Women, myocardial infarction, and dementia in the very old, Neurology, 40, 1102, 10.1212/WNL.40.7.1102 Bales, 1997, Lack of apolipoprotein E dramatically reduces amyloid beta-peptide deposition, Nat. Genet., 17, 263, 10.1038/ng1197-263 Beffert, 1998, Beta-amyloid peptides increase the binding and internalization of apolipoprotein E to hippocampal neurons, J. Neurochem., 70, 1458, 10.1046/j.1471-4159.1998.70041458.x Beffert, 1999, Apolipoprotein E isoform-specific reduction of extracellular amyloid in neuronal cultures, Brain Res. Mol. Brain Res., 68, 181, 10.1016/S0169-328X(99)00073-X Beffert, 1996, Apolipoprotein E, plaques, tangles and cholinergic dysfunction in Alzheimer's disease, Ann. N. Y. Acad. Sci., 777, 166, 10.1111/j.1749-6632.1996.tb34415.x Beffert, 1998, ApoE associated with lipid has a reduced capacity to inhibit beta-amyloid fibril formation, Neuroreport, 9, 3321, 10.1097/00001756-199810050-00031 Bjorkhem, 1998, Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation, J. Lipid Res., 39, 1594, 10.1016/S0022-2275(20)32188-X Bjorkhem, 2004, Brain cholesterol: long secret life behind a barrier, Arterioscler. Thromb. Vasc. Biol, 10.1161/01.ATV.0000120374.59826.1b Blennow, 1999, Genetic testing for Alzheimer's disease: how close is reality?, Curr. Opin. Psychiatry, 12, 487, 10.1097/00001504-199907000-00019 Blumenthal, 2000, Statins: effective antiatherosclerotic therapy, Am. Heart J., 139, 577, 10.1016/S0002-8703(00)90033-4 Bodovitz, 1996, Cholesterol modulates alpha-secretase cleavage of amyloid precursor protein, J. Biol. Chem., 271, 4436, 10.1074/jbc.271.8.4436 Bonarek, 2000, Relationships between cholesterol, apolipoprotein E polymorphism and dementia: a cross-sectional analysis from the PAQUID study, Neuroepidemiology, 19, 141, 10.1159/000026249 Bonn, 2002, Simvastatin, an HMG-CoA reductase inhibitor, induces the synthesis and secretion of apolipoprotein AI in HepG2 cells and primary hamster hepatocytes, Atherosclerosis, 163, 59, 10.1016/S0021-9150(01)00754-7 Borroni, 2004, Intronic CYP46 polymorphism along with ApoE genotype in sporadic Alzheimer disease: from risk factors to disease modulators, Neurobiol. Aging, 25, 747, 10.1016/j.neurobiolaging.2003.08.004 Boyles, 1989, A role for apolipoprotein E, apolipoprotein A–I, and low density lipoprotein receptors in cholesterol transport during regeneration and remyelination of the rat sciatic nerve, J. Clin. Invest., 83, 1015, 10.1172/JCI113943 Brookmeyer, 1998, Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset, Am. J. Public Health, 88, 1337, 10.2105/AJPH.88.9.1337 Brown, 1993, Lipid lowering and plaque regression. New insights into prevention of plaque disruption and clinical events in coronary disease, Circulation, 87, 1781, 10.1161/01.CIR.87.6.1781 Brown, 1993, Plasma lipid, lipoprotein cholesterol, and apoprotein distributions in selected US communities. The Atherosclerosis Risk in Communities (ARIC) Study, Arterioscler. Thromb., 13, 1139, 10.1161/01.ATV.13.8.1139 Caramelli, 1999, Increased apolipoprotein B serum concentration in Alzheimer's disease, Acta Neurol. Scand., 100, 61, 10.1111/j.1600-0404.1999.tb00724.x Chalmers, 2004, APOE promoter, ACE1 and CYP46 polymorphisms and beta-amyloid in Alzheimer's disease, Neuroreport, 15, 95, 10.1097/00001756-200401190-00019 Corder, 1993, Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families, Science, 261, 921, 10.1126/science.8346443 Courtney, 2004, Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial, Lancet, 363, 2105, 10.1016/S0140-6736(04)16499-4 Crisby, 2001, Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for plaque stabilization, Circulation, 103, 926, 10.1161/01.CIR.103.7.926 Cucchiara, 2001, Use of statins in CNS disorders, J. Neurol. Sci., 187, 81, 10.1016/S0022-510X(01)00529-9 Czyzewski, 2001, Lipid metabolism parameters in patients with Alzheimer's disease and their first degree relatives, Acta Neurobiol. Exp. (Wars.), 61, 21 Davignon, 1999, Low-density lipoprotein-independent effects of statins, Curr. Opin. Lipidol., 10, 543, 10.1097/00041433-199912000-00010 DeMattos, 2001, Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer's disease, Proc. Natl. Acad. Sci. U.S.A., 98, 8850, 10.1073/pnas.151261398 Desai, 2002, Genetic variation in the cholesterol 24-hydroxylase (CYP46) gene and the risk of Alzheimer's disease, Neurosci. Lett., 328, 9, 10.1016/S0304-3940(02)00443-3 Eckert, 2001, Differential effects of lovastatin treatment on brain cholesterol levels in normal and apoE-deficient mice, Neuroreport, 12, 883, 10.1097/00001756-200104170-00003 Ehehalt, 2003, Amyloidogenic processing of the Alzheimer {beta}-amyloid precursor protein depends on lipid rafts, J. Cell Biol., 160, 113, 10.1083/jcb.200207113 Erkinjuntti, 1988, Is determination of plasma lipids useful in the differentiation of multi-infarct dementia from Alzheimer's disease?, Compr. Gerontol. [A], 2, 1 Eto, 1988, Familial hypercholesterolemia and apolipoprotein E4, Atherosclerosis, 72, 123, 10.1016/0021-9150(88)90072-X Ettinger, 1992, Lipoprotein lipids in older people. Results from the Cardiovascular Health Study, Circulation, 86, 858, 10.1161/01.CIR.86.3.858 Frears, 1999, The role of cholesterol in the biosynthesis of beta-amyloid, Neuroreport, 10, 1699, 10.1097/00001756-199906030-00014 Furman, 2004, Rosuvastatin reduces MMP-7 secretion by human monocyte-derived macrophages: potential relevance to atherosclerotic plaque stability, Atherosclerosis, 174, 93, 10.1016/j.atherosclerosis.2004.01.009 Galbete, 2000, Cholesterol decreases secretion of the secreted form of amyloid precursor protein by interfering with glycosylation in the protein secretory pathway, Biochem. J., 348, 307, 10.1042/bj3480307 Giubilei, 1990, Serum lipoprotein pattern variations in dementia and ischemic stroke, Acta Neurol. Scand., 81, 84, 10.1111/j.1600-0404.1990.tb00936.x Goedert, 1993, Tau protein and the neurofibrillary pathology of Alzheimer's disease, Trends Neurosci., 16, 460, 10.1016/0166-2236(93)90078-Z Goedert, 1988, Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau, Proc. Natl. Acad. Sci. U.S.A., 85, 4051, 10.1073/pnas.85.11.4051 Gustafson, 2003, An 18-year follow-up of overweight and risk of Alzheimer disease, Arch. Intern. Med., 163, 1524, 10.1001/archinte.163.13.1524 Haass, 1993, Cellular processing of beta-amyloid precursor protein and the genesis of amyloid beta-peptide, Cell, 75, 1039, 10.1016/0092-8674(93)90312-E Hajjar, 2002, The impact of the use of statins on the prevalence of dementia and the progression of cognitive impairment, J. Gerontol. A Biol. Sci. Med. Sci., 57, 414, 10.1093/gerona/57.7.M414 Hartmann, 1994, Apolipoprotein E and cholesterol affect neuronal calcium signalling: the possible relationship to beta-amyloid neurotoxicity, Biochem. Biophys. Res. Commun., 200, 1185, 10.1006/bbrc.1994.1576 Heart Protection Study Collaborative Group, 2002. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360, 7–22. Heber, 1987, Low density lipoprotein receptor regulation and the cellular basis of atherosclerosis: implications for nutritional and pharmacologic treatment of hypercholesterolemia, Am. J. Cardiol., 60, 4G, 10.1016/0002-9149(87)90585-6 Hebert, 1997, Cholesterol lowering with statin drugs, risk of stroke, and total mortality. An overview of randomized trials, JAMA, 278, 313, 10.1001/jama.1997.03550040069040 Hernandez-Perera, 1998, Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells, J. Clin. Invest., 101, 2711, 10.1172/JCI1500 Hernandez-Perera, 2000, Involvement of Rho GTPases in the transcriptional inhibition of preproendothelin-1 gene expression by simvastatin in vascular endothelial cells, Circ. Res., 87, 616, 10.1161/01.RES.87.7.616 Hofman, 1997, Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study, Lancet, 349, 151, 10.1016/S0140-6736(96)09328-2 Holtzman, 2000, Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease, Proc. Natl. Acad. Sci. U.S.A., 97, 2892, 10.1073/pnas.050004797 Honig, 2003, Stroke and the risk of Alzheimer disease, Arch. Neurol., 60, 1707, 10.1001/archneur.60.12.1707 Howland, 1998, Modulation of secreted beta-amyloid precursor protein and amyloid beta-peptide in brain by cholesterol, J. Biol. Chem., 273, 16576, 10.1074/jbc.273.26.16576 Jick, 2000, Statins and the risk of dementia, Lancet, 356, 1627, 10.1016/S0140-6736(00)03155-X Jula, 2002, Effects of diet and simvastatin on serum lipids, insulin, and antioxidants in hypercholesterolemic men: a randomized controlled trial, JAMA, 287, 598, 10.1001/jama.287.5.598 Jurevics, 1995, Cholesterol for synthesis of myelin is made locally, not imported into brain, J. Neurochem., 64, 895, 10.1046/j.1471-4159.1995.64020895.x Kabbara, 2004, Exclusion of CYP46 and APOM as candidate genes for Alzheimer's disease in a French population, Neurosci. Lett., 363, 139, 10.1016/j.neulet.2004.03.066 Kalmijn, 2000, Metabolic cardiovascular syndrome and risk of dementia in Japanese–American elderly men. The Honolulu–Asia aging study, Arterioscler. Thromb. Vasc. Biol., 20, 2255, 10.1161/01.ATV.20.10.2255 Kawahara, 2001, Intracellular calcium changes in neuronal cells induced by Alzheimer's beta-amyloid protein are blocked by estradiol and cholesterol, Cell. Mol. Neurobiol., 21, 1, 10.1023/A:1007168910582 Kidd, 1963, Paired helical filaments in electron microscopy of Alzheimer's disease, Nature, 197, 192, 10.1038/197192b0 Kilsdonk, 1995, Cellular cholesterol efflux mediated by cyclodextrins, J. Biol. Chem., 270, 17250, 10.1074/jbc.270.29.17250 Kim, 2002, Low cholesterol, cognitive function and Alzheimer s disease in a community population with cognitive impairment, J. Nutr. Health Aging, 6, 320 Kivipelto, 2001, Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study, BMJ, 322, 1447, 10.1136/bmj.322.7300.1447 Kojro, 2001, Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the alpha-secretase ADAM 10, Proc. Natl. Acad. Sci. U.S.A., 98, 5815, 10.1073/pnas.081612998 Kolsch, 2002, Polymorphism in the cholesterol 24S-hydroxylase gene is associated with Alzheimer's disease, Mol. Psychiatry, 7, 899, 10.1038/sj.mp.4001109 Kurochkin, 1994, Alzheimer's beta-amyloid peptide specifically interacts with and is degraded by insulin degrading enzyme, FEBS Lett., 345, 33, 10.1016/0014-5793(94)00387-4 Kuusisto, 1997, Association between features of the insulin resistance syndrome and Alzheimer's disease independently of apolipoprotein E4 phenotype: cross sectional population based study, BMJ, 315, 1045, 10.1136/bmj.315.7115.1045 Kwak, 2003, Reduced connexin43 expression inhibits atherosclerotic lesion formation in low-density lipoprotein receptor-deficient mice, Circulation, 107, 1033, 10.1161/01.CIR.0000051364.70064.D1 Laufs, 2000, Atorvastatin upregulates type III nitric oxide synthase in thrombocytes, decreases platelet activation, and protects from cerebral ischemia in normocholesterolemic mice, Stroke, 31, 2442, 10.1161/01.STR.31.10.2442 Launer, 2000, Midlife blood pressure and dementia: the Honolulu–Asia aging study, Neurobiol. Aging, 21, 49, 10.1016/S0197-4580(00)00096-8 Lehtonen, 1986, High-density lipoprotein cholesterol levels of very old people in the diagnosis of dementia, Age Ageing, 15, 267, 10.1093/ageing/15.5.267 Leibson, 1997, Risk of dementia among persons with diabetes mellitus: a population-based cohort study, Am. J. Epidemiol., 145, 301, 10.1093/oxfordjournals.aje.a009106 Lennernas, 1997, Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. similarities and differences, Clin. Pharmacokinet., 32, 403, 10.2165/00003088-199732050-00005 Lesser, 2001, Elevated serum total and LDL cholesterol in very old patients with Alzheimer's disease, Dement. Geriatr. Cogn. Disord., 12, 138, 10.1159/000051248 Li, G., Higdon, R., Kukull, W.A., Peskind, E., Van Valen Moore, K., Tsuang, D., van Belle, G., McCormick, W., Bowen, J.D., Teri, L., Schellenberg, G.D., Larson, E.B., 2004. Statin therapy and risk of dementia in the elderly: a community-based prospective cohort study. Neurology. 9; 63 (9),1624–1628. Locatelli, 2002, Reduction of plasma 24S-hydroxycholesterol (cerebrosterol) levels using high-dosage simvastatin in patients with hypercholesterolemia: evidence that simvastatin affects cholesterol metabolism in the human brain, Arch. Neurol., 59, 213, 10.1001/archneur.59.2.213 Lomnitski, 1997, Reduced levels of antioxidants in brains of apolipoprotein E-deficient mice following closed head injury, Pharmacol. Biochem. Behav., 56, 669, 10.1016/S0091-3057(96)00412-1 Lutjohann, 2000, Plasma 24S-hydroxycholesterol (cerebrosterol) is increased in Alzheimer and vascular demented patients, J. Lipid Res., 41, 195, 10.1016/S0022-2275(20)32052-6 Maron, 2000, Current perspectives on statins, Circulation, 101, 207, 10.1161/01.CIR.101.2.207 Michikawa, 2000, Apolipoprotein E exhibits isoform-specific promotion of lipid efflux from astrocytes and neurons in culture, J. Neurochem., 74, 1008, 10.1046/j.1471-4159.2000.0741008.x Mielke, 2005, Elevated total cholesterol levels in late-life associated with a reduced risk of dementia, Neurology, 64, 1689, 10.1212/01.WNL.0000161870.78572.A5 Muckle, 1985, High-density lipoprotein cholesterol in differential diagnosis of senile dementia, Lancet, 1, 1191, 10.1016/S0140-6736(85)92866-1 Nawawi, 2003, Reduction in serum levels of adhesion molecules, interleukin-6 and C-reactive protein following short-term low-dose atorvastatin treatment in patients with non-familial hypercholesterolemia, Horm. Metab. Res., 35, 479, 10.1055/s-2003-41805 Notkola, 1998, Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer's disease, Neuroepidemiology, 17, 14, 10.1159/000026149 Octave, 1995, The amyloid peptide precursor in Alzheimer's disease, Acta Neurol. Belg., 95, 197 Ott, 1997, Atrial fibrillation and dementia in a population-based study. The Rotterdam Study, Stroke, 28, 316, 10.1161/01.STR.28.2.316 Ott, 1999, Diabetes mellitus and the risk of dementia: the Rotterdam Study, Neurology, 53, 1937, 10.1212/WNL.53.9.1937 Papassotiropoulos, 2002, 24S-hydroxycholesterol in cerebrospinal fluid is elevated in early stages of dementia, J. Psychiatr. Res., 36, 27, 10.1016/S0022-3956(01)00050-4 Peila, 2002, Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: the Honolulu–Asia aging study, Diabetes, 51, 1256, 10.2337/diabetes.51.4.1256 Petrovitch, 2000, Midlife blood pressure and neuritic plaques, neurofibrillary tangles, and brain weight at death: the HAAS. Honolulu–Asia aging study, Neurobiol. Aging, 21, 57 Pitas, 1987, Lipoproteins and their receptors in the central nervous system. Characterization of the lipoproteins in cerebrospinal fluid and identification of apolipoprotein B,E(LDL) receptors in the brain, J. Biol. Chem., 262, 14352, 10.1016/S0021-9258(18)47945-8 Poirier, 2002, Apolipoprotein E: a novel therapeutic target for the treatment of Alzheimer's disease, Adv. Behav. Biol., 1, 36 Puglielli, 2001, Acyl-coenzyme A: cholesterol acyltransferase modulates the generation of the amyloid beta-peptide, Nat. Cell Biol., 3, 905, 10.1038/ncb1001-905 Qiu, 2003, Pulse pressure and risk of Alzheimer disease in persons aged 75 years and older: a community-based, longitudinal study, Stroke, 34, 594, 10.1161/01.STR.0000060127.96986.F4 Racchi, 1997, Secretory processing of amyloid precursor protein is inhibited by increase in cellular cholesterol content, Biochem. J., 322, 893, 10.1042/bj3220893 Refolo, 2000, Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model, Neurobiol. Dis., 7, 321, 10.1006/nbdi.2000.0304 Refolo, 2001, A cholesterol-lowering drug reduces beta-amyloid pathology in a transgenic mouse model of Alzheimer's disease, Neurobiol. Dis., 8, 890, 10.1006/nbdi.2001.0422 Reiman, 2001, Declining brain activity in cognitively normal apolipoprotein E epsilon 4 heterozygotes: a foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease, Proc. Natl. Acad. Sci. U.S.A., 98, 3334, 10.1073/pnas.061509598 Reitz, 2004, Relation of plasma lipids to Alzheimer disease and vascular dementia, Arch. Neurol., 61, 705, 10.1001/archneur.61.5.705 Rocchi, 2003, Causative and susceptibility genes for Alzheimer's disease: a review, Brain Res. Bull., 61, 1, 10.1016/S0361-9230(03)00067-4 Rockwood, 2002, Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people, Arch. Neurol., 59, 223, 10.1001/archneur.59.2.223 Rodriguez, 2002, Use of lipid-lowering drugs in older adults with and without dementia: a community-based epidemiological study, J. Am. Geriatr. Soc., 50, 1852, 10.1046/j.1532-5415.2002.50515.x Romas, 1999, APOE genotype, plasma lipids, lipoproteins, and AD in community elderly, Neurology, 53, 517, 10.1212/WNL.53.3.517 Rudel, 2001, Acyl coenzyme A: cholesterol acyltransferase types 1 and 2: structure and function in atherosclerosis, Curr. Opin. Lipidol., 12, 121, 10.1097/00041433-200104000-00005 Runz, 2002, Inhibition of intracellular cholesterol transport alters presenilin localization and amyloid precursor protein processing in neuronal cells, J. Neurosci., 22, 1679, 10.1523/JNEUROSCI.22-05-01679.2002 4S-Study-Group, 1994. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344, 1383–1389. Sabo, 2001, The Alzheimer amyloid precursor protein (APP) and FE65, an APP-binding protein, regulate cell movement, J. Cell Biol., 153, 1403, 10.1083/jcb.153.7.1403 Scacchi, 1998, DNA polymorphisms of apolipoprotein B and angiotensin I-converting enzyme genes and relationships with lipid levels in Italian patients with vascular dementia or Alzheimer's disease, Dement. Geriatr. Cogn. Disord., 9, 186, 10.1159/000017045 Schneider, 1990, Familial hypercholesterolemia: dissection of a receptor disease, Z. Kardiol., 79, 3 Schonknecht, 2002, Cerebrospinal fluid 24S-hydroxycholesterol is increased in patients with Alzheimer's disease compared to healthy controls, Neurosci. Lett., 324, 83, 10.1016/S0304-3940(02)00164-7 Scott, 2001, Statins for the prevention of Alzheimer's disease, Cochrane Database Syst. Rev., CD003160 Shepherd, J., Blauw, G.J., Murphy, M.B., Bollen, E.L., Buckley, B.M., Cobbe, S.M., Ford, I., Gaw, A., Hyland, M., Jukema, J.W., Kamper, A.M., Macfarlane, P.W., Meinders, A.E., Norrie, J., Packard, C.J., Perry, I.J., Stott, D.J., Sweeney, B.J., Twomey, C., Westendorp, R.G.; PROSPER study group. PROspective Study of Pravastatin in the Elderly at Risk, 2002. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 360, 1623–1630. Siest, 2000, Apolipoprotein E polymorphism and serum concentration in Alzheimer's disease in nine European centres: the ApoEurope study. ApoEurope Group, Clin. Chem. Lab. Med., 38, 721, 10.1515/CCLM.2000.102 Simons, 2000, How cells handle cholesterol, Science, 290, 1721, 10.1126/science.290.5497.1721 Simons, 1998, Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons, Proc. Natl. Acad. Sci. U.S.A., 95, 6460, 10.1073/pnas.95.11.6460 Simons, 2002, Treatment with simvastatin in normocholesterolemic patients with Alzheimer's disease: a 26-week randomized, placebo-controlled, double-blind trial, Ann. Neurol., 52, 346, 10.1002/ana.10292 Sing, 1985, Role of the apolipoprotein E polymorphism in determining normal plasma lipid and lipoprotein variation, Am. J. Hum. Genet., 37, 268 Sjögren, 2003, Treatment with simvastatin in patients with Alzheimer's disease lowers both α- and β-cleaved APP. Dementia, Geriatr. Cogn. Disord., 16, 25, 10.1159/000069989 Skoog, 1996, 15-Year longitudinal study of blood pressure and dementia, Lancet, 347, 1141, 10.1016/S0140-6736(96)90608-X Small, 2000, Is APOE–epsilon4 a risk factor for cognitive impairment in normal aging?, Neurology, 54, 2082, 10.1212/WNL.54.11.2082 Small, 1994, A heparin-binding domain in the amyloid protein precursor of Alzheimer's disease is involved in the regulation of neurite outgrowth, J. Neurosci., 14, 2117, 10.1523/JNEUROSCI.14-04-02117.1994 Smith, 1998, Apolipoprotein E genotype influences cognitive ‘phenotype’ in patients with Alzheimer's disease but not in healthy control subjects, Neurology, 50, 355, 10.1212/WNL.50.2.355 Sparks, 1990, Cortical senile plaques in coronary artery disease, aging and Alzheimer's disease, Neurobiol. Aging, 11, 601, 10.1016/0197-4580(90)90024-T Sparks, 1993, Temporal sequence of plaque formation in the cerebral cortex of non-demented individuals, J. Neuropathol. Exp. Neurol., 52, 135, 10.1097/00005072-199303000-00006 Sparks, 1994, Induction of Alzheimer-like beta-amyloid immunoreactivity in the brains of rabbits with dietary cholesterol, Exp. Neurol., 126, 88, 10.1006/exnr.1994.1044 Sparks, 1995, Increased incidence of neurofibrillary tangles (NFT) in non-demented individuals with hypertension, J. Neurol. Sci., 131, 162, 10.1016/0022-510X(95)00105-B Sparks, 2004, Benefit of atorvastatin in the treatment of Alzheimer's disease, Montreal Staehelin, 1999, Apolipoprotein E genotypes and cognitive functions in healthy elderly persons, Acta Neurol. Scand., 100, 53, 10.1111/j.1600-0404.1999.tb00723.x Stamler, 1988, Dietary cholesterol and human coronary heart disease. The epidemiologic evidence, Arch. Pathol. Lab. Med., 112, 1032 Strittmatter, 1995, Apolipoprotein E and Alzheimer disease, Proc. Natl. Acad. Sci. U.S.A., 92, 4725, 10.1073/pnas.92.11.4725 Suzuki, 1994, High tissue content of soluble beta1–40 is linked to cerebral amyloid angiopathy, Am. J. Pathol., 145, 452 Takemoto, 2001, Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors, Arterioscler. Thromb. Vasc. Biol., 21, 1712, 10.1161/hq1101.098486 Tan, 2003, Plasma total cholesterol level as a risk factor for Alzheimer disease: the Framingham Study, Arch. Intern. Med., 163, 1053, 10.1001/archinte.163.9.1053 Tanaka, 2004, Anti-apoptotic effect of atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, on cardiac myocytes through protein kinase C activation, Clin. Exp. Pharmacol. Physiol., 31, 360, 10.1111/j.1440-1681.2004.04010.x Tomlinson, B., Henderson, G., 1976. Some quantitative cerebral findings in normal and demented old people. Neurobiology of Aging. G.S. Terry RD. Raven Press, New York. Tomlinson, 1984, Ageing and the dementias, 951 Tremollieres, 1999, Coronary heart disease risk factors and menopause: a study in 1684 French women, Atherosclerosis, 142, 415, 10.1016/S0021-9150(98)00252-4 Tun, 2002, Lipid rafts play an important role in A beta biogenesis by regulating the beta-secretase pathway, J. Mol. Neurosci., 19, 31, 10.1007/s12031-002-0007-5 Vaughan, 1996, Statins do more than just lower cholesterol, Lancet, 348, 1079, 10.1016/S0140-6736(96)05190-2 Wassmann, 2002, Cellular antioxidant effects of atorvastatin in vitro and in vivo, Arterioscler. Thromb. Vasc. Biol., 22, 300, 10.1161/hq0202.104081 Williams, 1998, Pravastatin has cholesterol-lowering independent effects on the artery wall of atherosclerotic monkeys, J. Am. Coll. Cardiol., 31, 684, 10.1016/S0735-1097(97)00537-8 Wischik, 1988, Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease, Proc. Natl. Acad. Sci. U.S.A., 85, 4506, 10.1073/pnas.85.12.4506 Wolozin, 2000, Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors, Arch. Neurol., 57, 1439, 10.1001/archneur.57.10.1439 Wolozin, 2004, Cholesterol, statins and dementia, Curr. Opin. Lipidol., 15, 667, 10.1097/00041433-200412000-00007 Wu, 2003, Brain region-dependent increases in beta-amyloid and apolipoprotein E levels in hypercholesterolemic rabbits, J. Neural. Transm., 110, 641, 10.1007/s00702-002-0809-1 Yaffe, 2002, Serum lipoprotein levels, statin use, and cognitive function in older women, Arch. Neurol., 59, 378, 10.1001/archneur.59.3.378 Yoshitake, 1995, Incidence and risk factors of vascular dementia and Alzheimer's disease in a defined elderly Japanese population: the Hisayama Study, Neurology, 45, 1161, 10.1212/WNL.45.6.1161 Zandi, P.P., Sparks, D.L., Khachaturian, A.S., Tschanz, J., Norton, M., Steinberg, M., Welsh-Bohmer, K.A., Breitner, J.C.; Cache County Study investigators, 2005. Do statins reduce risk of incident dementia and Alzheimer disease? The Cache County Study. Arch. Gen. Psychiatry. 62 (2), 217–224.