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In the century since the neuronal inclusions [neurofibrillary tangles (NFTs); Fig. 1] and extracellular protein aggregates (Aft plaques; Fig. 1) that form the pathological hallmarks of Alzheimer's disease (AD) were described, our knowledge of all aspects of AD has grown markedly. AD is uniformly progressive and ultimately results in debilitating cognitive impairment. In the early stages, the impairment may only be apparent on neuropsychological testing; however, by end stage, few functions above the automatic remain unaffected (Forstl and Kurz, 1999) | ALZHEIMER S DISEASE ITS DIAGNOSIS AND PATHOGENESIS Jillian J. Kril1 Centre for Education and Research on Ageing Concord Hospital Department of Medicine The University of Sydney Concord New South Wales Australia 2139 and Department of Pathology The University of Sydney Sydney New South Wales Australia 2006 Glenda M. Halliday Prince of Wales Medical Research Institute Randwick New South Wales Australia 2031 I. Introduction II. Diagnostic Issues A. Xf Plaques and NFTs for Pathological Diagnosis B. Evaluation of Other Pathologies c. Clinical Correlates of AD Pathology D. Reproducibility of Current Clinical Diagnostic Protocols E. Summary III. Pathogenesis A. Brain Atrophy B. Neuronal Loss c. Xfi Deposition D. NFT Formation E. Mechanisms of Degeneration F. Summary IV. Genetic Influences A. Dominant Inheritance B. Genetic Risk Factors c. Summary V. Inflammation and Anti-inflammatory Drugs VI. Estrogen Therapy VII. Vascular Pathology in AD A. Vascular Risk Factors B. Summary References Author to whom correspondence should be addressed. INTERNATIONAL REVIEW OF 167 Copyright 2001 by Academic Press. NEUROBIOLOGY VOL. 48 All rights of reproduction in any form reserved. 0074 7742 01 35.00 168 JILLIAN J. KRIL AND GLENDA M. HALLIDAY I. Introduction In the century since the neuronal inclusions neurofibrillary tangles NFTs Fig. 1 and extracellular protein aggregates AjS plaques Fig. 1 that form the pathological hallmarks of Alzheimer s disease AD were described our knowledge of all aspects of AD has grown markedly. AD is uniformly progressive and ultimately results in debilitating cognitive impairment. In the early stages the impairment may only be apparent on Clinicopathological diagnosis Lesion type her NFT diseases Inft m Ap plaques a . Lewy bodies . Clinical diagnosis 9 other dementias Fig. 1. The major pathologies resulting in dementia are neurofibrillary tangles NFTs top left A i plaques top center and Lewy bodies top right arrow . Diagnosis of AD was previously based on .
