Vulnerability of the Neuronal Cytoskeleton in Aging and Alzheimer Disease: Widespread Involvement of All Three Major Filament Systems

Abstract

Alzheimer disease (AD) is the commonest cause of dementia in the elderly (for recent reviews, see Chiu, 1989; Henderson & Finch, 1989; Katzman et al., 1988). As a consequence of the increasing number of people living beyond the seventh decade, AD has become the fourth leading cause of death in the United States. Despite the recognition of AD and the brain pathology associated with it more than 80 years ago (Alzheimer, 1907), the pathogenesis and etiology of AD remain enigmatic. Several reasons account for this such as (1) the complexity and limited understanding of the central nervous system (CNS); (2) an incomplete definition of AD and variants thereof; (3) the lack of animal models for hypothesis testing; (4) overlap between early AD and normal aging as well as between AD and other neurodegenerative diseases. For example, patients with idiopathic Parkinson disease (PD) frequently develop cognitive impairments, AD patients often exhibit extrapyramidal signs, and diminished olfaction is observed in AD and PD subjects (Chiu, 1989; Doty et al., 1987, 1989).