Is Alzheimer's disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics

Masters, 1985, Amyloid plaque core protein in Alzheimer disease and Down syndrome, Proc Natl Acad Sci USA, 82, 4245, 10.1073/pnas.82.12.4245 Johnson, 2001, Presenilin-1- associated abnormalities in regional cerebral perfusion, Neurology, 56, 1545, 10.1212/WNL.56.11.1545 Roth, 1955, The natural history of mental disorder in old age, J Mental Sci, 101, 281, 10.1192/bjp.101.423.281 McKhann, 1984, Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of the Department of Health and Human Services Task Force on AD, Neurology, 34, 939, 10.1212/WNL.34.7.939 1994, 138 Selkoe, 1991, The molecular pathology of Alzheimer's disease, Neuron, 6, 487, 10.1016/0896-6273(91)90052-2 Glenner, 1984, Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein, Biochem Biophys Res Commun, 120, 885, 10.1016/S0006-291X(84)80190-4 Hardy, 2002, The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics, Science, 297, 353, 10.1126/science.1072994 Joseph, 2001, Copernicus revisited: amyloid beta in Alzheimer's disease, Neurobiol Aging, 22, 161 Davis, 1997, The 'amyloid' cascade hypothesis of AD: decoy or real McCoy?, Trends Neurosci, 20, 558 Neve, 1998, Alzheimer's disease: a re-examination of the amyloid hypothesis, Trends Neurosci, 21, 15, 10.1016/S0166-2236(97)01168-5 Bishop, 2002, The amyloid hypothesis: let sleeping dogmas lie?, Neurobiol Aging, 23, 1101, 10.1016/S0197-4580(02)00050-7 de la Torre, 2002, Alzheimer's disease: how does it start?, J Alz Dis, 4, 497, 10.3233/JAD-2002-4606 de la Torre, 2002, Alzheimer's disease as a vascular disorder: nosological evidence, Stroke, 33, 1152, 10.1161/01.STR.0000014421.15948.67 Terry, 1991, Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment, Ann Neurol, 4, 572, 10.1002/ana.410300410 Arriagada, 1992, Neurofibrillar tangles but not senile plaques parallel duration and severity of Alzheimer's disease, Neurology, 42, 631, 10.1212/WNL.42.3.631 Braak, 1996, Age, neurofibrillary changes, A-beta and onset of Alzheimer's disease, Neurosci Lett, 210, 87, 10.1016/0304-3940(96)12668-9 Braak, 1997, Frequency of stages of Alzheimer-related lesions in different age categories, Neurobiol Aging, 4, 351, 10.1016/S0197-4580(97)00056-0 Davis, 1999, Alzheimer neuropathologic alterations in aged cognitively normal subjects, J Neuropathol Exp Neurol, 58, 376, 10.1097/00005072-199904000-00008 Hatanpää, 1996, Neuronal activity and early neurofibrillary tangles in Alzheimer's disease, Ann Neurol, 40, 411, 10.1002/ana.410400310 DeCarli, 1992, Post-mortem regional neurofibrillary tangle densities, but not senile plaque densities are related to regional cerebral metabolic rates for glucose during life in Alzheimer disease patients, Neurodegeneration, 1, 11 Ji, 1998, Apolipoprotein E polymorphism in patients with Alzheimer's disease, vascular dementia and ischemic cerebrovascular disease, Dement Geriatr Cogn Disord, 5, 243, 10.1159/000017068 Kalaria, 2000, The role of cerebral ischemia in Alzheimer's disease, Neurobiol Aging, 21, 321, 10.1016/S0197-4580(00)00125-1 Hsiao, 1996, Correlative memory deficits, A-beta elevation, and amyloid plaques in transgenic mice, Science, 274, 99, 10.1126/science.274.5284.99 Irizarry, 1997, PPSw transgenic mice develop age-related A beta deposits and neuropil abnormalities, but no neuronal loss in CA1, J Neuropathol Exp Neurol, 56, 965, 10.1097/00005072-199709000-00002 Koistinaho, 2001, Specific spatial learning deficits become severe with age in beta -amyloid precursor protein transgenic mice that harbor diffuse beta -amyloid deposits but do not form plaques, Proc Natl Acad Sci USA, 98, 14675, 10.1073/pnas.261562998 Hsiao, 1995, Age-related CNS disorder and early death in transgenic FVB-N mice overexpressing Alzheimer amyloid precursor proteins, Neuron, 15, 1203, 10.1016/0896-6273(95)90107-8 Austin, 2003, Short-term beta-amyloid vaccinations do not improve cognitive performance in cognitively impaired APP + PS1 mice, Behav Neurosci, 117, 478, 10.1037/0735-7044.117.3.478 Selkoe, 2000, Toward a comprehensive theory for alzheimer's disease: hypothesis, Alzheimer's disease is caused by the cerebral accumulation and cytotoxicity of amyloid β protein, Ann NY Acad Sci, 924, 17, 10.1111/j.1749-6632.2000.tb05554.x Robinson, 2002, The search for an amyloid solution, Science, 298, 962, 10.1126/science.298.5595.962 Steinberg, 2002, Companies halt first Alzheimer vaccine trial, Scientist, 16, 22 Smith, 2002, Predicting the failure of amyloid-beta vaccine, Lancet, 359, 1864, 10.1016/S0140-6736(02)08695-6 Perry, 2000, Amyloid-beta junkies, Lancet, 355, 757, 10.1016/S0140-6736(05)72173-5 Leigh, 2003, The production of amyloid-beta peptide Is a critical requirement for the viability of central neurons, J Neurosci, 23, 5531, 10.1523/JNEUROSCI.23-13-05531.2003 Robinson, 2002, Abeta as a bioflocculant: implications for the amyloid hypothesis of Alzheimer's disease, Neurobiol Aging, 23, 1051, 10.1016/S0197-4580(01)00342-6 de la Torre, 1993, Can disturbed brain microcirculation cause Alzheimer's disease?, Neurol Res, 15, 146, 10.1080/01616412.1993.11740127 1997, Cerebrovascular pathology in Alzheimer's disease: proceedings of a conference, East Rutherford, New Jersey, Nov 12–15, 1996, Ann NY Acad Sci, 826, 1 2000, Vascular factors in Alzheimer's disease, Ann NY Acad Sci, 903, 1 2000, Vascular pathophysiology in Alzheimer's disease, Neurobiol Aging, 21, 153, 10.1016/S0197-4580(99)00110-4 2002, Alzheimer's disease: vascular etiology and pathology, Ann NY Acad Sci, 977, 1 Meyer, 2000, Risk factors for cerebral hypoperfusion, mild cognitive impairment and dementia, Neurobiol Aging, 21, 161, 10.1016/S0197-4580(00)00136-6 Skoog, 1999, The interaction between vascular disorders and Alzhemer's disease, 523 Skoog, 2000, Hypertension and related factors in the etiology of Alzheimer's disease, Ann NY Acad Sci, 977, 29, 10.1111/j.1749-6632.2002.tb04796.x Breteler, 2000, Vascular involvement in cognitive decline and dementia: epidemiologic evidence from the Rotterdam Study and the Rotterdam Scan Study, Ann NY Acad Sci, 903, 457, 10.1111/j.1749-6632.2000.tb06399.x Pohjasvaara, 1998, Clinical determinants of poststroke dementia, Stroke, 29, 75, 10.1161/01.STR.29.1.75 Snowdon, 1997, Brain infarction and the clinical expression of Alzheimer's disease: the Nun study, JAMA, 277, 813, 10.1001/jama.1997.03540340047031 Kalaria, 2002, Small vessel disease and Alzheimer's dementia: pathological considerations, Cerebrovasc Dis, 13, 48, 10.1159/000049150 White, 2002, Cerebrovascular pathology and dementia in autopsied Honolulu-Asia Aging Study participants, Ann NY Acad Sci, 977, 9, 10.1111/j.1749-6632.2002.tb04794.x Tatemichi, 1994, Risk of dementia after stroke in a hospitalized cohort: results of a longitudinal study, Neurology, 44, 1885, 10.1212/WNL.44.10.1885 Schmidt, 1992, Comparison of magnetic resonance imaging in Alzheimer's disease, vascular dementia and normal aging, Eur Neurol, 32, 164, 10.1159/000116816 Pasquier, 2000, Relevance of white matter changes to pre- and poststroke dementia, Ann NY Acad Sci, 903, 466, 10.1111/j.1749-6632.2000.tb06400.x Suter, 2002, Cerebral hypoperfusion generates cortical watershed microinfarcts in Alzheimer disease, Stroke, 33, 1986, 10.1161/01.STR.0000024523.82311.77 Vermeer, 2003, Silent brain infarcts and the risk of dementia and cognitive decline, N Engl J Med, 348, 1215, 10.1056/NEJMoa022066 Kwan, 1999, Effects of subcortical cerebral infarction on cortical glucose metabolism and cognitive function, Arch Neurol, 56, 809, 10.1001/archneur.56.7.809 Vermeer, 2002, Prevalence and risk factors of silent brain infarcts in the population-based Rotterdam Scan Study, Stroke, 33, 21, 10.1161/hs0102.101629 O'Connell, 1998, Atrial fibrillation and cognitive function: case-control study, J Neurol Neurosurg Psychiatry, 65, 386, 10.1136/jnnp.65.3.386 Vermeer, 2003, Incidence and risk factors of silent brain infarcts in the population-based Rotterdam Scan Study, Stroke, 34, 392, 10.1161/01.STR.0000052631.98405.15 Alter, 1986, Standardized incidence ratios of stroke: a worldwide review, Neuroepidemiology, 5, 148, 10.1159/000110824 Aronson, 1990, Women, myocardial infarction, and dementia in the very old, Neurology, 40, 1102, 10.1212/WNL.40.7.1102 Ott, 1997, Atrial fibrillation and dementia in a population-based study: the Rotterdam Study, Stroke, 28, 316, 10.1161/01.STR.28.2.316 Polidori, 2001, Heart disease and vascular risk factors in the cognitively impaired elderly: implications for Alzheimer's dementia, Aging (Milan), 13, 231 Sparks, 1997, Coronary artery disease, hypertension, ApoE, and cholesterol: a link to Alzheimer's disease?, Ann NY Acad Sci, 826, 128, 10.1111/j.1749-6632.1997.tb48466.x Newman, 2001, Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery, N Eng J Med, 344, 395, 10.1056/NEJM200102083440601 Brillman, 1993, Central nervous system complications in coronary artery bypass graft surgery, Neurol Clin, 11, 475, 10.1016/S0733-8619(18)30164-6 Selnes, 1999, Determinants of cognitive change after coronary artery bypass surgery: a multifactorial problem, Ann Thorac Surg, 67, 1669, 10.1016/S0003-4975(99)00258-1 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 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 Aliev, 2002, Atherosclerotic lesions and mitochondria DNA deletions in brain microvessels as a central target for the development of human AD and AD-like pathology in aged transgenic mice, Ann NY Acad Sci, 977, 45, 10.1111/j.1749-6632.2002.tb04798.x de la Torre, 2000, Evidence that Alzheimer's disease is a microvascular disorder: role of constitutive nitric oxide, Brain Res Rev, 34, 119, 10.1016/S0165-0173(00)00043-6 Lunn, 1999, Impact of carotid endarterectomy upon cognitive functioning: a systematic review of the literature, Cerebrovasc Dis, 9, 74, 10.1159/000015901 de la Torre, 2003, Hippocampal nitric oxide upregulation precedes memory loss and Aβ1–40 accumulation after chronic brain hypoperfusion in rats, Neurol Res, 25, 635, 10.1179/016164103101201931 Bakker, 2000, Cognitive disorders in patients with occlusive disease of the carotid artery: a systematic review of the literature, J Neurol, 247, 669, 10.1007/s004150070108 Sinforiani, 2001, Neuropsychological changes after carotid endarterectomy, Funct Neurol, 16, 329 Heyer, 1998, Neuropsychometric changes in patients after carotid endarterectomy, Stroke, 29, 1110, 10.1161/01.STR.29.6.1110 de la Torre, 1999, Critical threshold cerebral hypoperfusion causes Alzheimer's disease, Acta Neuropathol, 98, 1, 10.1007/s004010051044 de la Torre, 2000, Critically-attained threshold of cerebral hypoperfusion: the CATCH hypothesis of Alzheimer's pathogenesis, Neurobiol Aging, 21, 331, 10.1016/S0197-4580(00)00111-1 de la Torre, 1997, Hemodynamic consequences of deformed microvessels in the brain in Alzheimer's disease, Ann NY Acad Sci, 826, 75, 10.1111/j.1749-6632.1997.tb48462.x Frankish, 2003, NSAIDs do not slow Alzheimer's progression, Lancet, 361, 1964, 10.1016/S0140-6736(03)13609-4 Knopman, 2003, Pharmacotherapy for Alzheimer's disease: 2002, Clin Neuropharmacol, 26, 93, 10.1097/00002826-200303000-00009 Gold, 2003, The lowdown on Ginkgo biloba, Sci Am, 288, 86, 10.1038/scientificamerican0403-86 de la Torre, 1997, Hemodynamic consequences of deformed microvessels in the brain in Alzheimer's disease, Ann NY Acad Sci, 826, 75, 10.1111/j.1749-6632.1997.tb48462.x Roland, 1985, Localization of cortical areas activated by thinking, J Neuropathol, 53, 1219 Ball, 2002, Prevention of brain aging and dementia, Clin Geriatr Med, 18, 485, 10.1016/S0749-0690(02)00027-7 de la Torre, 1993, Brain blood-flow restoration "rescues" chronically damaged rat CA1 neurons, Brain Res, 623, 6, 10.1016/0006-8993(93)90003-6 De Jong, 1999, Cerebral hypoperfusion yields capillary damage in hippocampus CA1 that correlates to spatial memory impairment, Neuroscience, 91, 203, 10.1016/S0306-4522(98)00659-9 Farkas, 2000, Pathological features of cerebral cortical capillaries are doubled in Alzheimer's disease and Parkinson's disease, Acta Neuropathol (Berl), 100, 395, 10.1007/s004010000195 De Jong, 1997, Cerebrovascular hypoperfusion: a risk factor for Alzheimer's disease? Animal model and postmortem human studies, Ann NY Acad Sci, 826, 56, 10.1111/j.1749-6632.1997.tb48461.x Aliev, 2003, Mitochondria and vascular lesions as a central target for the development of Alzheimer's disease and Alzheimer disease-like pathology in transgenic mice, Neurol Res, 25, 665, 10.1179/016164103101201977 Mancardi, 1980, Thickening of the basement membrane of cortical capillaries in Alzheimer's disease, Acta Neuropathol, 49, 79, 10.1007/BF00692225 Buée, 1997, Brain microvascular changes in Alzheimer's disease and other dementias, Ann NY Acad Sci, 826, 7, 10.1111/j.1749-6632.1997.tb48457.x Kawamoto, 2002, Transplantation of endothelial progenitor cells for therapeutic neovascularization, Cardiovasc Radiat Med, 3, 221, 10.1016/S1522-1865(03)00082-9 Asahara, 1997, Isolation of putative progenitor endothelial cells for angiogenesis, Science, 275, 964, 10.1126/science.275.5302.964 Takahashi, 1999, Ischemia- and cytokine-induced mobilization of bone marrow- derived endothelial progenitor cells for neovascularization, Nat Med, 5, 434, 10.1038/8462 Kocher, 2001, Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function, Nat Med, 7, 430, 10.1038/86498 Luttun, 2002, Vascular progenitors: from biology to treatment, Trends Cardiovasc Med, 12, 88, 10.1016/S1050-1738(01)00152-9 Hill, 2003, Circulating endothelial progenitor cells, vascular function, and cardiovascular risk, N Engl J Med, 348, 593, 10.1056/NEJMoa022287 Asahara, 1999, Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization, Circ Res, 85, 221, 10.1161/01.RES.85.3.221 Shah, 2000, Mild cognitive impairment: when is it a precursor of Alzheimer's disease?, Geriatrics, 55, 65 Johnson, 2000, Perfusion abnormalities in prodromal Alzheimer's disease, Neurobiol Aging, 21, 289, 10.1016/S0197-4580(00)00137-8 Kogure, 2000, Longitudinal evaluation of early Alzheimer's disease using brain perfusion SPECT, J Nucl Med, 41, 1155 Okamura, 2000, Prediction of progression in patients with mild cognitive impairment using IMP-SPECT, Nippon Ronen Igakkai Zasshi, 37, 974, 10.3143/geriatrics.37.974 Rodriguez, 2000, Hippocampal perfusion in mild cognitive impairment, Psychiatry Res, 100, 65, 10.1016/S0925-4927(00)00071-8 De Santi, 2001, Hippocampal formation glucose metabolism and volume losses in MCI and AD, Neurobiol Aging, 22, 529, 10.1016/S0197-4580(01)00230-5 de Leon, 2001, Prediction of cognitive decline in normal elderly subjects with 2-[(18)F] fluoro-2-deoxy-D-glucose/positron-emission tomography (FDG/PET), Proc Natl Acad Sci USA, 98, 10966, 10.1073/pnas.191044198 2000, Alzheimer's disease: a compendium of current theories, Ann NY Acad Sci, 924, 1