Chapter 7 Neuronal Aging and Alzheimer's Disease

Abstract

This chapter determines whether the available data support the specific hypothesis that pathological neuronal aging, with an increase in neuronal cell death, is involved in the etiology of Alzheimer's disease (AD). A comparison between normal aging and AD shows that most AD-specific hallmarks seem to be a part of a continuum: tangles and amyloid plaques accumulate with normal aging. Changes characteristic of both apoptosis and necrosis are found in the AD-affected brain, indicating that both processes may be fundamental mechanisms leading to disruption of neuronal function in AD. It is proposed that aging-related disruption of neuronal plasma membrane structure, and thereby interference with normal cellular homeostasis, may be among the first and most disastrous events in the induction of normal neuronal apoptosis in the AD etiology. Secondary tangle formation, Aβ production, and amyloid formation may lead to more widespread cell death and inflammatory reactions. It is suggested that changes in conformation andor integrity of proteins of the anion exchanger family, with the concomitant changes in regulation of intracellular pH and in membrane-cytoskeleton interaction, are likely to be essential elements in the neuronal aging process. Understanding the mechanisms that underlie the Alzheimer-related changes in anion exchangers proteins may help elucidate both physiological and pathological neuronal aging processes.