ALZHEIMER''''S DISEASE: ITS DIAGNOSIS AND PATHOGENESIS - PART 5 doc

ALZHEIMER'S DISEASE 207 Hu,J., Miyatake, E, Aizu, Y, Nakagawa, H., Nakamura, S., Tamaoka, A., Takahash, R., Urakami, ~, and Shoji, M. (1999). Angiotensin-converting enzyme genotype is associated with Alzheimer disease in the Japanese population. Neurosci. Lett. 277, 65-67. Hyman, B. T., and Trojanowski, J. Q. (1997). Editorial on consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment ofAlzheimer Disease.J. Neuropathol. Exp. NeuroL 56, 1095-1097. Iraizoz, I., Guijarro,J. L., Gonzalo, L. M., and de Lacalle, S. (1999). Neuropathological changes in the nucleus basalis correlate with clinical measures of dementia. Acta Neuropathol. 98, 186-196. Irina, A., Seppo, H., Arto, M., Paavo, St., R., and Hilkka, S. (1999). fl-Amyloid load is not influenced by the severity of cardiovascular disease in aged and demented patients. Stroke 30, 613-618. Irizarry, M. C., McNamara, M., Fedorchak, K., Hsiao, K., and Hyman, B. T. (1997a). APP-sw transgenic mice develop age-related A~ deposits and neuropil abnormalities, but no neu- ronal loss in CA1.J. Neuropathol. Exp. Neurol. 56, 965-973. Irizarry, M. C., Soriano, E, McNamara, M., Fedorchak, K., Hsiao, K., and Hyman, B. T. (1997b). A/~ deposition is associated with neuropil changes, but not with overt neuronal loss in the human amyloid precursor protein V717f (PDAPP) transgenic mouse.J. Neurosa. 17, 7053- 7059. lwata, N., Tsubuki, S., Takai, Y., Watanabe, K., Sekiguchi, M., Hosoki, E., Kawashima-Morishima, M., Lee, H J., Hama, E., Sekine-Aizawa, Y, and Saido, T. C. (2000). Identification of the major Afll-42-degrading catabolic pathway in brain parenchyma: Suppression leads to biochemical and pathological deposition. Nat. Med. 6, 143-150. iwatsubo, T., Saido, T. C., Mann, D. M. A., Lee, V. M Y, and Trojanowski,J. Q. (1996). Full-length amyloid-fl(1-42(43)) and amino-terminally modified and truncated amyloid-f142(43) de- posit in diffuse plaques. Am.J. Pathol. 149, 1823-1830. Jack, C. R., Petersen, R. C., Xu, Y C., O'Brien, E C., Waring, S. C., Tangalos, E. G., Smith, G. E., Ivnik, R.J., Thibodeau, S. N., and Kokmen, E. (1998). Hippocampal atrophy and apolipoprotein E genotype are independently associated with Alzheimer's disease. Ann. Neurol. 43, 303-310. Jellinger, K. A., Bancher, C., and Fischer, E (1995). Interlaboratory comparison ofneuropathol- ogy assessment in Alzheimer's disease.J. Neuropathol. Exp. Neurol. 54, 129-130. Jorm, A. E (1990). "The Epidemiology of Alzheimer's Disease and Related disorders." Chapman and Hall, London. Juottonen, K., Laakso, M. P., Insausti, R., Lehtovirta, M., Pitk~men, A., Partanen, K., and Soininen, H. (1998a). Volumes of the entorhinal and perirhinal cortices in Alzheimer's disease. Neurobiol. Aging 19, 15-22. Juottonen, K~, Lehtovirta, M., Helisahni, S., Riekkinen, Sr., E J., and Soininen, H. (1998b). Major decrease in the volume of the entorhinal cortex in patients with Alzheimer's dis- ease carrying the apolipoprotein E epsilon4 allele. J. Neurol. Neurosurg. Psychiatry 65, 322- 327. Kalaria, R. N. (2000). The role of cerebral ischemia in Alzheimer's disease. Neurobiol. Aging 21, 321-330. Kalaria, R. N., and Hedera, E (1995). Differential degeneration of the cerebral microvascula- ture in Alzheimer's disease. Neuroreport 6, 477-480. Katzman, R. (1993). Education and the prevalence of dementia and Alzheimer's disease. Neurology 43, 13-20. Katzman, R. (1994). Apolipoprotein E and Alzheimer's disease. Cu~ Opin. Neurobiol. 4, 703- 707. 208 JILLIAN J. KRIL AND GLENDA M. HALLIDAY Kawas, C., Resnick, S., Morrison, A., Brookmeyer, R., Corrada, M., Zonderman, A., Bacal, C., Donnell Lingle, D., and Metter, E. (1997). A prospective study of estrogen replacement therapy and the risk of developing Alzheimer's disease: The Baltimore Longitudinal Study of Aging. Neurology 48, 1517-1521. Kaye, J. A., Swihart, T., Howieson, D., Dame, A., Moore, M. M., Karnos, T., Camicioli, R., Ball, M., Oken, B., and Sexton, G. (1997). Volume loss of the hippocampus and temporal lobe in healthy elderly persons destined to develop dementia. Neurology 48, 1297-1304. Kehoe, E G., Russ, C., McIlory, S., Williams, H., Holmans, E, Holmes, C., Liolitsa, D., Vahidassr, D., Powell, J., McGleenon, B., Liddell, M., Plomin, R., Dynan, K., Williams, N., Neal, J., Cairns, N.J., Wilcock, G., Passmore, E, Lovestone, S., Williams,J, and Owen, M.J. (1999). Variation in DCP1, encoding ACE, is associated with susceptibility to Alzheimer disease. Nat. Genet. 21, 71-72. Khachaturian, Z. S. (1985). Diagnosis of Alzheimer's disease. Arch. Neurol. 42, 1097-1105. Khan, M. A., Kushner, I., and Weitkamp, L. R. (1983). Genetics of HLA-associated disease: Rheumatoid arthritis. Tissue Antigens 22, 182-185. Kokmen, E., Whisnant, J. E, O'Fallon, W. M., Chu, C. E, and Beard, C. M. (1996). Dementia after ischaemic stroke: A population based study in Rochester, Minnesota, (1960-1984). Neurology 46, 154-159. Kosaka, K., Yoshimura, M., Ikeda, K., and Budka, H. (1984). Diffuse type of Lewy body disease: Progressive dementia with abundant cortical Lewy bodies and senile changes of varying degree a new disease? Clin. Neuropathol. 3, 185-192. Kosunen, O., Soininen, H., Paljarvi, L., Heinonen, O., Talasniemi, S., and Riekkinen, Sr., E J. (1996). Diagnostic accuracy of Alzheimer's disease: a neuropathological study. Acta Neu~vpathoL 91,185-193. Kril,J.J., and Halliday, G. M. (1999). Brain shrinkage in alcoholics: a decade on and what have we learned? Prog~. Neurobiol. 58, 381-387. Kril,J.J., Patel, S., Harding, A.J., and Halliday, G. M. (2000). Neuron loss in the hippocampus in Alzheimer's disease is not solely as a result of tangle formation. Brain Pathol. 10, 787- 788. Kukall, W. A., Larson, E. B., Reifler, B. V., Lampe, T. H., Yerby, M., and Hughes, J. (1990). Interrater reliability of Alzheimer's disease diagnosis. Neurology 40, 257-260. Kuusisto,J., Koivisto, K., Mykkanen, L., Helkala, E. L., Vanhanen, M., Hanninen, T., Kervinen, K., Kesaniemi, Y A., Riekkinen, EJ., and Laakso, M. (1997). Association between features of the insulin resistence syndrome and Alzheimer's disease independently of apolipoprotein E4 phenotype: Cross sectional population based study. Br. Med.J. 315, 1045-1049. Kwok,J. B.J., Taddei, K., Hallupp, M., Fischer, C., Brooks, W. S., Broe, G. A., Hardy,J., Fulham, M.J., Nicholson, G. A., Stell, R., St. George-Hyslop, E H., Fraser, E E., Kakulas, B., Clarnette, R., Relkin, N., Gandy, S. E., Schofield, E R., and Martins, R. N. (1997). Two novel (M233T and R278T) presenilin-1 mutations in early-onset Alzheimer's disease anmd preliminary evidence for association of presenilin-1 mutations with a novel phenotype. Neuroreport 8, 1537-1542. Ladner, C.J., and Lee, J. M. (1998). Pharmacological drug treatment of Alzheimer's disease: The cholinergic hypothesis revisited. J. Neuropathol. Exp. Neurol. 57, 719-731. Landen, M., Thorsell, A., Wallin, A., and Blennow, K. (1996). The apolipoprotein E allele e4 does not correlate with the number of senile plaques or neurofibrillary tangles in patients with Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry 61, 352-356. Lassmann, H., Bancher, C., Breitschopf, H., Wegiel, J., Bobinski, M., Jellinger, K., and Wisniewski, H. M. (1995). Cell death in Alzheimer's disease evaluated by DNA fragmenta- tion in situ. Acta Neuropathologica 89, 35-41. ALZHEIMER'S DISEASE 209 Lee, M S., Kwon, Y. T., Li, M., Peng,J., Friedlander, R. M., and Tsai, L H. (2000). Neurotoxicity induces cleavage of p35 to p25 by calpain. Nature 405, 360-364. Lehtovirta, M., Laakso, M. E, Soininen, H., Helisalmi, S., Mannermaa, A., Helkala, E L., Partanen, K., Ryyn/men, M., Vainio, E, Hartikainen, P., and Riekkinen, Sr., P.J. (1995). Volumes of hippocampus, amygdala and frontal lobe in Alzheimer patients with different apolipoprotein E genotypes. Neuroscience 67, 65-72. Letenneur, L., Gilleron, V., Commenges, D., Helmer, C., Orgogozo, J. M., and Dartigues, J. E (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. Leuba, G., and Kraftsik, R. (1994). Visual cortex in Alzheimer's disease: occurrence of neuronal death and glial proliferation, and correlation with pathological hallmarks. Neuro&'ol. Aging 15, 29-43. Lin, B., Schmidt-Kastner, R., Busto, R., and Ginsberg, M. D. (1999). Progressive parenchymal deposition ofbeta-amyloid protein in rat brain following global ischaemia. Acta Neuropathol. 97, 359-368. Lopez, O. L., Swihart, A. A., Becker, J. T., Reinmuth, O. M., Reynolds, C. E, Rezek, D. L., and Daly, E L. (1990). Reliability of NINCDS-ADRDA clinical criteria for the diagnosis of Alzheimer's disease. Neurology 40, 1517-1522. Lu, D. C., Rabizadeh, S., Chandra, S., Shayya, R. E, Ellerby, L. M., Ye, X., Salvesen, G. S., Koo, E. H., and Bredesen, D. E. (2000). A second cytotoxic proteolytic peptide derived from amyloid t-protein precursor. Nat. Med. 6, 397-404. Lu, K. E, Hanes, S. D., and Hunter, T. (1996). A human peptidyl-prolyl isomerase essential for regulation of mitosis. Nature 380, 544-547. Lu, E-J., Wulf, G., Zhou, X. Z., Davies, E, and Lu, K. E (1999). The prolyl isomerase Pinl restores the function ofAlzheimer-associated phosphorylated tau protein. Nature 399, 784- 788. Lue, L E, Kuo, Y-M., Roher, A. E., Brachova, L., Shen, Y, Sue, L., Beach, T., Kurth,J. H., Rydel, R. E., and Rogers, J. (1999). Soluble amyloid fl peptide concentration as a predictor of synaptic change in Alzheimer's disease. Am. J. Pathol. 155, 853-862. MacGowan, S. H., Wilcock, G. K., and Scott, M. (1998). Effect of gender and apolipoprotein E genotype on the response to anticholinesterase therapy in Alzheimer's disease. Int. ~L Ge~atr. Psych. 13, 625-630. Mackenzie, I. R. A., and Munoz, D. G. (1998). Nonsteroidal anti-inflammatory drug use and Alzheimer-type pathology in aging. Neurology 50, 986-990. Maki, E M., and Resnick, S. M. (2000). Longitudinal effects of estrogen replacement therapy on PET cerebral blood flow and cognition. Neurobiol. Aging21, 373-383. Martin, E. M., Wilson, R. S., Penn, R. D., Fox, J. H., Clasen, R. A., and Savoy, S. M. (1987). Cortical biopsy results in Alzheimer's disease: Correlation with cognitive deficits. Neurology 37, 1201-1204. Matsumae, M., Kikinis, R., Morocz, I. A., Lorenzo, A. V., Sandor, T., Albert, M. S., Black, E M., and Jolesz, E A. (1996). Age-related changes in intracranial compartment volumes in normal adults assessed by magnetic resonance imaging. J. Neurosurg. 84, 982-991. Mattiace, L. A., Davies, P., and Dickson, D. W. (1990). Detection of HLA-DR microglia in the human brain is a function of both clinical and technical factors. Am.J. Pathol. 136, 1101- 1114. McCulla, M. M., Coats, M., van Fleet, N., Duchek, J., Grant, E., and Morris, J. C. (1989). Reliability of clinical nurse specialists in the staging of dementia. Arch. Neurol. 46, 1210- 1211. 210 JILLIAN J. KRIL AND GLENDA M. HALLIDAY McGeer, P. L., and McGeer, E. G. (1995). The inflammatory response system of brain: Impli- cations for therapy of Alzheimer and other neurodegenerative diseases. Brain Res. Rev. 21, 195-218. McGeer, P. L., Schulzer, M., and McGeer, E. G. (1996). Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: A review of 17 epidemiological studies. Neurology 47, 425-432. McKee, A. C., Kosik, K. S., and Kowall, N. W. (1991). Neuritic pathology and dementia in Alzheimer's disease. Ann. NeuroL 30, 156-165. McKeith, I. G., Galasko, D., Kosaka, K., Perry, E., Dickson, D. W., Hansen, L. A., Salmon, D. P., Lowe, J., Mirra, S. S., Byrne, E.J., Lennox, G., Quinn, N. E, Edwardson, J. A., Ince, E G., Bergeron, C., Burns, A., Miller, B. L., Lovestone, S., Collerton, D., Jansen, E. N. H., Ballard, C., de Vos, R. A. I., Wilcock, G. K., Jellinger, K. A., and Perry, R. H. (1996). Consensus guidelines for the clinical and pathologic diagnosis of Dementia with Lewy Bodies (DLB): Report of the consortium on DLB international workshop. Neurology 47, 1113-1124. McKeith, I. G., Perry, E. K., and Perry, R. H. (1999). Report of the second dementia with Lewy body international workshop. Diagnosis and treatment. Consortium on Dementia with Lewy Bodies. Neurology 53, 902-905. McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., and Stadlan, E. M. (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 Taskforce on Alzheimer's disease. Neurology 34, 939-944. Middleton, D., Mawhinney, H., Curran, M. D., Edwardson,J. A., Perry, R., McKeith, I., Morris, C., Ince, E G., and Neill, D. (1999a). Frequency of HLA-A and B alleles in early and late-onset Alzheimer's disease. Neurosci. Lett. 262, 140-142. Middleton, D., Vahidssr, D. M., Savage, D. A., Mawhinney, H., Curran, M. D., and Passmore, E A. (1999b). HLA-DR alleles are not associated with late-onset sporadic Alzheimer's disease. Alz. Rep. 2, 147-149. Miller, A. K. H., and Corsellis, J. A. N. (1977). Evidence for a secular increase in human brain weight during the past century. Ann. Human Biol. 4, 253-257. Mirra, S. S., Gearing, M., McKeel, D. W., Crain, B.J., Hughes,J. E, van Belle, G., and Heyman, A. (1994). Interlaboratory comparison of neuropathology assessments in Alzheimer's dis- ease: A study of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). J. Neuropathol. Exp. Neurol. 53, 303-315. Mirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, E S., Hughes,J. E, van Belle, G., and Berg, L. (1991). The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardisation of the neuropathologic assessment of Alzheimer's disease. Neurology 41,479-486. Mochizuki, A., Tamaoka, A., Shimohata, A., Komatsuzaki, Y, and Shoji, S. (2000). Abeta42- positive non-pyramidal neurons around amyloid plaques in Alzheimer's disease. Lancet 355, 42-43. Morris, C. M., Benjamin, R., Leake, A., McArthur, E K., Candy, J. M., Ince, E G., Tolwik, A., Bjertness, E., and Edwardson, J. A. (1995). Effect of apolipoprotein E genotype on Alzheimer's disease neuropathology in a cohort of elderly Norwegians. Neurosci. Lett. 201, 45-47. Morris, J. c. (1993). The Clinical Dementia Rating (CDR) : Current version and scoring rules. Neurology 43, 2412-2414. Morris,J. C. (1999). Is Alzheimer's disease inevitable with age? Lessons from clinicopathologic studies of healthy aging and very mild Alzheimer's disease. J. Clin. Invest. 104, 1171-1173. Morris, J. c., Heyman, A., Mohs, R. C., Hughes, J. P., van Belle, G., Fillenbaum, G., Mellits, ALZHEIMER'S DISEASE 211 E. D., and Clark, C. (1989). The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's dis- ease. Neurology 39, 1159-1165. Morris,J. C., McKeel, D. W., Fulling, K., Torack, R. M., and Berg, L. (1988). Validation of clinical diagnostic criteria for Alzheimer's disease. Ann. Neurol. 14, 17-22. Morris,J. C., Storandt, M., McKeel,Jr., D. W., Rubin, E. H., Price,J. L., Grant, E. A., and Berg, L. (1996). Cerebral amyloid deposition and diffuse plaques in "normal" aging: Evidence for presymptomatic and very mild Alzheimer's disease. Neurology 46, 707-719. Morsch, R., Simon, W., and Coleman, E D. (1999). Neurons may live for decades with neu- rofibrillary tangles. J. NeuroL Neurosurg. Psychiatry 58, 188-197. Mouton, E R., Martin, L.J., Calhoun, M. E., Dal Forno, G., and Price, D. L. (1998). Cognitive decline strongly correlates with cortical atrophy in Alzheimer's dementia. Neurobiol. Aging 19, 371-377. Mucke, L., Masliah, E., Yu, G Q., Mallory, M., Rockenstein, E. M., Tatsuno, G., Hu, K., Kholodenko, D., Johnson-Wood, K., and McConlogue, L. (2000). High-level neuronal expression of A/31-42 in wild-type human amyloid protein precursor transgenic mice: Synaptotoxicity without plaque formation. J. Neurosci. 20, 4050~t058. Mueller, E. A., Moore, M. M., Kerr, D. C., Sexton, G., Camicioli, R. M., Howieson, D. B., Quinn, J. E, and Kaye,J. A. (1998). Brain volume preserved in healthy elderly through the eleventh decade. Neurology 51, 1555-1562. Mulnard, R. A., Cotman, C. W., Kawas, C., van Dyck, C. H., Sano, M., Doody, R., Koss, E., Pfeiffer, E.,Jin, S., Gamst, A., Grundman, M., Thomas, R., and Thal, L.J. (2000). Estrogen replacement therapy for treatment of nfild to moderate Alzheimer disease: A randomized controlled trial. Alzheimer's Disease Cooperative Study.J.A.M.A. 283, 1007-1015. Munoz, D. G., Ganapathy, G. R., Eliasziw, M., and Hachinski, V. (2000). Educational attainment and socioeconomic status of patients with autopsy-confirmed Alzheimer disease. Arch. Neu- rol. 57, 85-89. Murphy, D. G., DeCarli, C., McIntosh, A. R., Daly, E., Mentis, M.J., Pietrini, E, Szczepanik, J., Schapiro, M. B., Grady, C. L., Horwitz, B., and Rapoport, S. I. (1996). Sex differences in human brain morphometry and metabolism: An in vivo quantitative magnetic reso- nance imaging and positron emission tomography study on the effect of aging. Arch. Gen. Psychiatry 53, 585-594. Nagy, Z., Esiri, M. M., Hindley, N.J.,Joachim, C., Morris, J. H., King, E. M F., McDonald, B., Litchfield, S., Barnetson, L., Jobst, K. A., and Smith, A. D. (1998). Accuracy of clinical eperational diagnostic criteria for Alzheimer's disease in relation to different pathological diagnostic protocols. Dement. Geriatr. Cogn. Disord. 9, 219-226. Nagy, Z., Esiri, M. M.,Jobst, IL A.,Johnston, C., Litchfield, S., Sim, E., and Smith, A. D. (1995). Influence of the apolipoprotein E genotype on amyloid deposition and neurofibrillary tangle formation in Alzheimer's disease. Neuroscience 69, 757-761. Nagy, Z., Esiri, M. M., Jobst, K. A., Morris, J. H., King, E. M E, McDonald, B., Joachim, C., Litchfield, S., Barnetson, L., and Smith, A. D. (1997a). The effects of additional pathology on the cognitive deficit in Alzheimer disease.J. Neuropathol. Exp. Neurol. 56, 165-170. Nagy, Z., Hindley, N.J., Braak, H., Braak, E., Yilmazer-Hanke, D. M., Schul~, C., Barnetson, L., King, E. M E,Jobst, K. A., and Smith, A. D. (1999). The progression of Alzheimer's disease from limbic regions to the neocortex: Clinical, radiological and pathological relationships. Dement. Geriatr. Cogn. Disord. 10, 115-120. Nagy, Z., Jobst, K. A., Esiri, M. M., Morris, J. H., King, E. M E, MacDonald, B., Litchfield, S., Barnetson, L., and Smith, A. D. (1996). Hippocampal pathology reflects memory deficit and brain imaging measurements in Alzheimer's disease: Clinicopathologic correlations using three sets of pathologic diagnostic criteria. Dementia 7, 76-81. 212 JILLIAN J. KRIL AND GLENDA M. HALLIDAY Nagy, Z., Vatter-Bittner, B., Braak, H., Braak, E., Yilmazer, D. M., Schultz, C., and Hanke, J. (1997b). Staging of Alzheimer-type pathology: An interrater-intrarater study. Dement. Geriatr. Cogn. Disord. 8, 248-251. Nakagawa, T., Zhu, H., Morishima, N., Li, E., Xu,J., Yanker, B. A., and Yuan,J. (2000). Caspase- 12 mediates endoplasmic reticulum-specific apoptosis and cytotoxicity by amyloid-fl. Nature 403, 98-103. Nathan, B. P., Bellosta, S., Sanan, D. A., Weisgraber, K. H., Mahley, R. W., and Pitas, R. E. (1994). Differential effects of apolipoproteins E3 and E4 on neuronal growth in vitro. Science264, 850-852. National Institute on Aging and Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Diagnosis of Alzheimer's Disease. (1997). Consensus recommen- dations for the postmortem diagnosis of Alzheimer's disease. Neurobiol. Aging 18(4S), S1-$3. Neill, D., Curran, M. D., Middleton, D., Mawhinney, H., Edwardson,J. A., McKeith, I., Ballard, C., Morris, C., Ince, E,Jaros, E., and Perry, R. (1999). Risk for Alzheimer's disease in older late-onset cases is associated with HLA-DRBI*3. Neurosci. Lett. 275, 137-140. Neve, R. L., and Robakis, N. K. (1998). Alzheimer's disease: A re-examination of the amyloid hypothesis. Trends Neurosci. 21, 15-19. Newell, K. L., Hyman, B. T., Growdon,J. H., and Hedley-Whyte, T. E. (1999). Application of the National Institute on Aging (NIA) Reagan Institute criteria for the neuropathological diagnosis ofAlzheimer disease.J. Neuropathol. Exp. Nenrol. 58, 1147-1155. Nijhawan, D., Honarpour, N., and Wang, X. (2000). Apoptosis in neural development and disease. Annu. Rev. Neurosci. 23, 73-87. Niki, E., and Nakano, M. (1990). Estrogens as antioxidants. Methods Enzymol. 186, 330-333. Ohm, T. G., Busch, C., and Bohl, J. (1997). Unbiased estimation of neuronal numbers in the human nucleus coeruleus during aging. Nenrobiol. Aging 18, 393-399. Ohm, T. G., Muller, H., Braak, H., and Bohl, J. (1995). Close-meshed prevalence rates of different stages as a tool to uncover the rate of Alzheimer's disease-related neurofibrillary changes. Neuroscience 64, 209-217. Ott, A., Stolk, R. P., van Harskamp, E, Pols, H. A. P., Hofman, A., and Breteler, M. M. B. (1999). Diabetes mellitus and the risk of dementia. The Rotterdam Study. Neurology 53, 1937- 1942. Overmyer, M., Helisalmi, S., Soininen, H., Laakso, M., Riekkinen, Sr., P., and Alafuzoff, I. (1999). Astrogliosis and the ApoE genotype. Dement. Geriatr. Cogn. Disord. 10, 252-257. Paganini-Hill, A., and Henderson, V. W. (1994). Estrogen deficiency and risk of Alzheimer's disease. Am.J. Epidemiol. 140, 256-261. Paganini-Hill, A., and Henderson, V. (1996). Estrogen replacement therapy and risk of Alzheimer's disease. Arch. Intern. Med. 156, 2213-2217. Pakkenberg, B., and Gundersen, H.J.G. (1997). Neocortical neuron number in humans: Effects of sex and age.J. Comp. NeuroL 384, 312-320. Pantoni, L., Garcia, J. H., and Brown, G. G. (1996). Vascular pathology in three cases of pro- gressive cognitive deterioration.J. Neurol. Sci. 135, 131-139. Patrick, G.N., Zukerberg, L., Nikolic, M., de la Monte, S., Dikkes, E, and Tsai, L.H. (1999). Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature 402, 615-622. Payami, H., Schellenberg, G. D., Zareparsi, S., Kaye,J., Sexton, G.J., Head, M. A., Matsuyama, S. S.,Jarvik, L. E, Miller, B., McManus, D. Q., Bird, T. D., Katzman, R., Heston, L., Norman, D., and Small, G. W. (1997). Evidence for an association of HLA-A2 allele with onset age of Alzheimer's disease. Neurology 49, 512-518. Pellegrini, L., Passer, B.J., Tabaton, M., Ganjei, J. K., and D'Adamio, L. (1999). Alternative, ALZHEIMER'S DISEASE 213 non-secretase processing of Alzheimer's fl-amyloid precursor protein during apoptosis by caspase-6 and-8.J. Biol. Chem. 272, 21011-21016. Peruzzi, P., von Euw, D., and Lacombe, P. (2000). Differentiated cerebrovascular effects of physostigmine and tacrine in cortical areas deafferented from the nucleus basalis magno- cellularis suggest involvement of basalocortical projections to microvessels. Ann. N. Y. Acad. Sci. 903, 394-406. Peters, A., Rosene, D. L., Moss, M. B., Kemper, T. L., Abraham, C. R., Tigges, J., and Albert, M. S. (1996). Neurobiological bases of age-related cognitive decline in rhesus monkey. J. Neuropathol. Exp. Neurol. 55, 861-874. Poirier, J., Delisle, M C., Quirion, R., Aubert, I., Farlow, M., Lahiri, D., Hui, S., Bertrand, P., Nalbantoglu, J., Gilfix, B. M., and Gauthier, S. (1995). Apolipoprotein E4 allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer's disease. Proc. Natl. Acad. Sci. USA 92, 12260-12264. Price,J. L., and Morris,J. C. (1999). Tangles and plaques in nondemented aging and "Preclin- ical" Alzheimer's disease. Ann. Neurol. 45, 358-368. Prince, M., Rabe-Hesketh, S., and Brennan, E (1998). Do antiarthritic drugs decrease the risk for cognitive decline? An analysis based on data from the MRC treatment trial of hypertension in older adults. Neurology 50, 374-379. Ravens,]. R. (1978). Vascular changes in the human senile brain. Adv. Neurol. 20, 487-501. Ray, W.J., Yao, M., Mumm, J., Schroeter, E. H., Saftig, P., Wolfe, M., Selkoe, D.J., Kopan, R., and Goate, A. M. (1999). Cell surface presenilin-1 participates in the gamma-secretase-like proteolysis of Notch. J. Biol. Chem. 274, 36801-36807. Raz, N., Gunning, F. M., Head, D., Dupuis, J. H., McQuain, J., Briggs, S. D., Loken, W. J., Thornton, A. E., and Acker, J. D. (1997). Selective aging of the human cerebral cortex observed in vivo: Differential vulnerability of the prefrontal gray matter. Cereb. Cortex 7, 268-282. Regeur, L. (2000). Increasing loss of brain tissue with increasing dementia: A stereological study of post-mortem brains from elderly females. Eur.J. Neurol. 7, 47-54. Regeur, L., Badsberg Jensen, G., Pakkenberg, H., Evans, S. M., and Pakkenberg, B. (1994). No global neocortical nerve cell loss in brains from patients with senile dementia of Alzheimer's type. Neurobiol. Aging 15, 347-352. Richard, E, Helbecque, N., Neuman, E., Guez, D., Levy, R., and Amouyel, E (1997). ApoE genotyping and response to drug treatment in Alzheimer's disease. Lancet 349, 539. Risse, S. C., Raskin, M. A., Nochlin, D., Sumi, S. M., Lampe, T. H., Bird, T. D., Cubberley, L., and Peskind, E. R. (1990). Neuropathological findings in patients with clinical diagnosis of probable Alzheimer's disease. Am. J. Psychiatry 147, 168-172. Rogers,J., Kirby, L. C., Hempleman, S. R., Berry, D. L., McGeer, P. L., Kaszniak, A. W., Zalinski, J., Cofield, M., Mansukhani, L., Willson, E, and Kogan, E (1993). Clinical trial of in- domethacin in Alzheimer's disease. Neurology 43, 1609-1611. Roher, A. E., Kuo, Y M., Potter, E E., Emmerling, M. R., Durham, R. A., Walker, D. G., Sue, L. I., Honer, W. G., and Beach, T. G. (2000). Cortical cholinergic denervation elicits vascular A beta deposition. Ann. N.Y. Acad. Sci. 903, 366-373. Roses, A. D. (1996). Apolipoprotein E in neurology. Cu~ Opin. Neurol. 9, 265-270. Rozemuller, J. M., van der Valk, E, and Eikelenboom, E (1992). Activated microglia and cere- bral amyloid deposits in Alzheimer's disease. Res. lmmunol. 143, 646-649. Rubin, E. H., Storandt, M., Miller, J. E, Kinscherf, D. A., Grant, E. A., Morris,]. C., and Berg, L. (1998). A prospective study of cognitive function and onset of dementia in cognitively healthy elders. Arch. Neurol. 55, 395-401. Saunders, A. M., Strittmatter, W.J., Schmechel, D., George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., Gusella,J. E, Crapper-MacLachlan, D. R., Alberts, M.J., Hulette, C., 214 JILLIAN J. KRIL AND GLENDA M. HALLIDAY Crain, B., Goldgaber, D., and Roses, A. D. (1993). Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. Neurology 43,1467-1472. Scharf, S., Mander, A., Ugoni, A., Vajda, E, and Christophidis, N. (1999). A double-blind placebo-controlled trial of diclofenac/misoprostol in Alzheimer's disease. Neurology 53, 197-201. Schenk, D. B., Seubert, P., Lieberburg, I., and Wallace, J. (2000). fl-peptide immunization. A possible new treatment for Alzheimer disease. Arch. Neurol. 57, 934-936. Schmechel, D. E., Saunders, A. M., Strittmatter, W.J., Crain, B.J., Hulette, C. M., Joo, S. H., Pericak-Vance, M. A., Goldgaber, D., and Roses, A. D. (1993). Increased amyloid beta- peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. Proc. Natl. Acad. Sci. USA 90, 9649-9653. Schwab, C., Schulzer, M., Steele, J. c., and McGeer, E L. (1999). On the survival time of a tangled neuron in the hippocampal CA4 region in parkinsonian dementia complex of Guam. Neurobiol. Aging20, 57-63. Schwab, C., Steele,J. C., and McGeer, E L. (1998). Pyramidal neuron loss is matched by ghost tangle increase in Guam parkinsonism-dementia hippocampus. Acta Neuropathol. 96, 409- 416. Selznick, L. A., Holtzman, D. M., Han, B. H., Gokden, M., Srinivasan, A. N., Johnson, Jr., E. M., and Roth, K. A. (1999). In situ immunodetection of neuronal caspase-3 activation in Alzheimer disease.J. Neuropathol. Exp. Neurol. 58, 1029-1026. Shear, E K., Sullivan, E. V., Mathalon, D. H., Lim, K. O., Davis, L. E, Yesavage,J. A., Tinklenberg, J. R., and Pfefferbaum, A. (1995). Longitudinal volumetric computed tomographic analysis of regional brain changes in normal aging and Alzheimer's disease. Arch. NeuroL 52, 392- 402. Shefer, V. E (1973). Absolute number of neurons and thickness of the cerebral cortex during aging, senile and vascular dementia, and Pick's and Alzheimer's disease. Zhurnal Nevropa- tologii i Psikhiatrii imeni S. S. Korsakova 1972;72:1024-1029. (Translated in Neurosci. Behav. Physiol. 6, 319-324.) Shi, J., Perry, G., Smith, M. A., and Friedland, R. P. (2000). Vascular abnormalitites: The insid- ious pathogenesis of Alzheimer's disease. Neurobiol. Aging 21,357-361. Simic, G., Kostovic, I., Winblad, B., and Bogdanovic, N. (1997). Volume and number of neurons of the human hippocampal formation in normal aging and Alzheimer's disease. J. Comp. Neurol. 379, 482-494. Skoog, I., Lernfelt, B., Landahl, S., Pahnertz, B., Andreasson, L A., Nilsson, L., Persson, G., Oden, A., and Svanborg, A. (1996). 15-Year longitudinal study of blood pressure and dementia. Lancet 347, 1141-1145. Smale, G., Nichols, N. R., Brady, D. R., Finch, C. E., and Horton,Jr., W. E. (1995). Evidence of apoptotic cell death in Alzheimer's disease. Exp. Neurol. 133, 225-230. Small, B.J., Fratiglioni, L., Viitanen, M., Winblad, B., and Backman, L. (2000). The course of cognitive impairment in preclinical Alzheimer disease: Three- and 6-year follow-up of a population-based sample. Arch. NeuroL 57, 839-844. Small, G. W., Ebeling, S. C., Matsuyama, S. S., heyman, A., Reisner, E. G., Renvoize, E. B., and Sulkava, R. (1991). Variable association of HLA-A2 in men with early-onset Alzheimer disease. Neurobiol. Aging 12, 375-377. Smith, A. D., and Jobst, K. A. (1996). Use of structural imaging to study the progression of Alzheimer's disease. Br. Med. Bull. 52, 575-586. Smith, C. D., Snowdon, D., and Markesbery, W. R. (2000). Periventricular white matter hyper- intensities on MRI: Correlation with neuropathologic findings.J. Neuroimaging 10, 13-16. Smith, M.J., Kwok, J. B.J., McLean, C. A., Kril, J.J., Broe, G. A., Nicholson, G. A., Cappai, R., Hallupp, M., Cotton, R. G. H., Masters, C. L., Schofield, E R., and Brooks, W. S. (2001). ALZHEIMER'S DISEASE 215 Variable phenotype of Alzheimer's disease with spastic paraparesis in a pedigree with a deletion of exon 9 of the presenilin 1 gene. Ann. Neurol. 49, 125-129. Snowdon, D. A., Greiner, L. H., Mortimer, J. A., Riley, K. P., Greiner, E A., and Markesbery, W. R. (1997). Brain infarction and the clinical expression of Alzheimer's disease. The Nun study.J.A.M.A. 277, 813-817. Sparks, D. L. (1997). Coronary artery disease, hypertension, ApoE, and cholesterol: A link to Alzheimer's disease? Ann. N.Y. Acad. Sci. 826, 128-146. Sparks, D. L., Hunsaker, J. C., Scheff, S. W., Kryscio, R.J., Henson,J. L., and Markesbery, W. R. (1990). Cortical senile plaques in coronary artery disease, aging and Alzheimer's disease. Neurobiol. Aging 11, 601-607. St. George-Hyslop, E H. (2000). Molecular genetics of Alzheimer's disease. Biol. Psychiatry 47, 183-199. Stadelmann, C., Deckwerth, T. L., Srinivasan, A., Bancher, C., Bruck, W., Jellinger, K., and Lassmann, H. (1999). Activation of caspase-3 in single neurons and autophagic granules of granulovacuolar degeneration in Alzheimer's disease. Evidence for apoptotic cell death. Am. J. Pathol. 155, 1459-1466. Stastny, P., Ball, E.J., Khan, M. A., Olsen, N.J., Pincus, T., and Gao, X. (1988). HLA-DR4 and other genetic markers in rheumatoid arthritis. Br. J. Rheumatol. 27 (Suppl. 2), 132-138. Stern, Y., Gurland, B., Tatemichi, T., Tang, M., Wilder, D., and Mayeaux, R. (1994). Influence of education and occupation on the in cidence of Alzheimer's disease. J.A.M.A. 271, 1004- 1010. Stevens, M., van Du!jn, C. M., de Knijff, P., van Broeckhoven, C., Heutink, E, Oostra, B. A., Niermeijer, M. E, and van Swieten, J. C. (1997). Apolipoprotein E gene and sporadic frontal lobe dementia. Neurology 48, 1526-1529. Stewart, W. E, Kawas, C., Corrada, M., and Metter, E.J. (1997). Risk of Alzheimer's disease and duration of NSAID use. Neurology 48, 626-632. Storey, E., and Cappai, R. (1999). The amyloid precursor protein of Alzheimer's disease and the A~ peptide. Neuropathol. Appl. Neurobiol. 25, 81-97. Strittmatter, W.J., and Roses, A. D. (1995). Apolipoprotein E and Alzheimer disease. Proc. Natl. Acad. Sci. USA 92, 4725-4727. Strittmatter, W.J., Weisgraber, K. H., Huang, D. Y., Dong, L. M., Salvesen, G. S., Pericak-Vance, M., Schmechel, D., Saunders, A. M., Goldgaber, D., and Roses, A. D. (1993). Binding of human apolipoprotein E to synthetic amyloid beta peptide: Isoform-specific effects and implications for late-onset Alzheimer disease. Proc. Natl. Acad. Sci. USA 90, 8098- 8102. Tapiola, T., Pirttila, T., Mikkonen, M., Mehta, E D., Alafuzoff, I., Koivisto, K., and Soininen, H. (2000). Three-year follow-up of cerebrospinal fluid tan, beta-amyloid 42 and 40 concen- trations in Alzheimer's disease. Neurosci. Lett. 280, 119-122. Terry, R. D., de Theresa, R., and Hansen, L. A. (1987). Neocortical cell counts in normal human adult aging. Ann. Neurol. 21,530-539. Thal, D. R., Arendt, T., Waldmann, G., Holzer, M., Zedlick, D., Rub, U., and Schober, R. (1998). Progression of neurofibrillary changes and PHF-tau in end-stage Alzheimer's disease is different from plaque and cortical microglial pathology. Neurobiol. Aging 19, 517-525. Tierney, M. C., Fisher, R. H., Lewis, A. J., Zorzitto, M. L., Snow, W. G., Reid, D. W., and Nieuwstraten, P. (1988). The NINCDS-ADRDA work group criteria for the clinical diagnosis of probable Alzheimer's disease: A clinicopathological study of 57 cases. Neu- rology 38, 359-364. Tohgi, H., Takahashi, S., Kato, E., Homma, A., Niina, R., Sasaki, K., Yonezawa, H., and Sasaki, M. (1997). Reduced size of right hippocampus in 39- to 80-year-old normal subjects carrying the apolipoprotein E e4 allele. Neurosci. Lett. 236, 21-24. 216 JILLIAN J. KRIL AND GLENDA M. HALLIDAY Tolnay, M., and Probst, A. (1999). Review: Tau protein pathology in Alzheimer's disease and related disorders. Neuropathol. Appl. Neurobiol. 25, 171-187. Tong, X. K., and Hamel, E. (1999). Regional cholinergic denervation of cortical microvessels and nitric oxide synthase-containing neurons in Alzheimer's disease. Neuroscience 92, 163- 175. Turner, R. S., Suzuki, N., Chyung, A. S. C., Younkin, S. G., and Lee, V. M. Y (1996). Amyloids beta(40) and beta(42) are generated intracellularly in cultured human neurons and their secretion increases with maturation. J. Biol. Chem. 271, 8966 8970. Unger, J., van Belle, G., and Heyman, A. (1999). Cross-sectional vs. longitudinal estimates of cognitive change in the non-demented elderly: A CERAD study.J. Am. G~ Soc. 47, 559-563. Uterman, G. (1994). The apolipoprotein E connection. Cu~ BioL 4, 362-365. Verkkoniemi, A., Somer, M., Rinne,J. O., Myllykangas, L., Crook, R., Hardy, J., Viitanen, M., Kalimo, H., and Haltia, M. (2000). Variant Alzheimer's disease with spastic paraparesis: Clinical characterization. Neurology 54, 1103-1109. Vincent, B., and Smith, J. D. (2000). Effect of estradiol on neuronal Swedish-mutated beta- amyloid precursor protein metabolism: Reversal by astrocytic cells. Biochem. Bi~phys. Res. Commun. 271, 82-85. Visser, P.J., Scheltens, E, Verhey, E R.J., Schmand, B., Launer, L.J.,Jolles, J., andJonker, C. (1999). Medial temporal lobe atrophy and memory dysfunction as predictors for dementia in subjects with mild cognitive impairment.J. Neurol. 246, 477-485. Vogels, O.J.M., Broere, C. A. J., Lak, H.J.T., Donkelaar, H. J. T., Nieuwenhuys, R., and Schultz, E M. (1990). Cell loss and shrinkage in the nucleus basalis of Meynert complex in Alzheimer's disease. Neurobiol. Aging 11, 3-13. Wahlund, L O., Julin, P., Lannfelt, L., Lindqvist, J., and Svensson, L. (1999). Inheritance of the ApoE epsilon4 allele increases the rate of brain atrophy in dementia patients. Dement. Geriatr. Cogn. Disord. 10, 262-268. Walker, D. G. (1998). Inflammatory markers in chronic neurodegenerative disorders with emphasis on Alzheimer's disease. In "Neuroinflammation: Mechanisms and Management" (P. L. Wood, ed.), pp. 61-90. Humana Press, Totowa, NJ. Wang, J., Dickson, D. W., Trojanowski, J. Q., and Lee, V. M Y. (1999). The levels of soluble versus insoluble brain Aft distinguish Alzheimer's disease from normal and pathologic aging. Exp. Neurol. 158, 328-337. Weldon, D. T., Rogers, S. D., Ghilardi, J. R., Finke, M. E, Cleary, J. P., O'Hare, E., Esler, W. E, Maggio, J. E., and Mantyh, E W. (1998). Fibrillar beta-amyloid induces microglial phagocytosis, expression of inducible nitric oxide synthase, and loss of a select population of neurons in the rat CNS in vivo.J. Neurosci. 18, 2161-2173. West, K. M. (1978). "Epidemiology of Diabetes and Its Vascular Complications." Elsevier, New York. West, M.J. (1993). Regionally specific loss of neurons in the aging human hippocampus. Neurobiol. Aging 14, 287-293. West, M.J., Coleman, E D., Flood, D. G., and Troncoso,J. C. (1994). Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease. Lancet 344, 769- 772. West, M.J., and Gundersen, H.J.G. (1990). Unbiased stereological estimation of the number of neurons in the human hippocampus. J. Comp. Neurol. 296, 1-22. Wilson, C. A., Doms, R. W., and Lee, V. M Y (1999). Intracellular APP processing and Aft production in Alzheimer's disease. J. Neuropathol. Exp. Neurol. 58, 787-794. Wolfe, M. S., De Los Angeles, J., Miller, D. D., Xia, W., and Selkoe, D.J. (1999). Are prese- nilins intramembrane-cleaving proteases? Implications for the molecular mechanism of Alzheimer's disease. Biochemistry 38, 11223-11230. . V. M Y, and Trojanowski,J. Q. (1996). Full-length amyloid-fl( 1-4 2(43)) and amino-terminally modified and truncated amyloid-f142(43) de- posit in diffuse plaques. Am.J. Pathol. 149, 182 3-1 830 Psych. 13, 62 5- 6 30. Mackenzie, I. R. A., and Munoz, D. G. (1998). Nonsteroidal anti-inflammatory drug use and Alzheimer-type pathology in aging. Neurology 50 , 98 6-9 90. Maki, E M., and Resnick,. Winblad, B., and Backman, L. (2000). The course of cognitive impairment in preclinical Alzheimer disease: Three- and 6-year follow-up of a population-based sample. Arch. NeuroL 57 , 83 9-8 44. Small,