Tau Phosphorylation and Dephosphorylation in the Pathogenesis of Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is the most common dementing illness among individuals over 60 years old, the most rapidly growing segment of the population in developed countries. The AD brain contains two conspicuous types of deposits, the extracellular senile or amyloid plaques and the intraneuronal neurofibrillary tangles (NFTs). NFTs and senile plaques (SPs) were first described by Alois Alzheimer in 1907 and their presence in large numbers has since been recognized as one of the major neuropathological characteristics of the disease that bears his name. NFTs are formed within nerve cells that degenerate during the course of the disease where they are found in the cell body, and related neurofibrillary lesions also are seen in abnormal neurites associated with amyloid plaques and within the neuropil threads (Alzheimer 1907; Braak et al. 1986). The relative insolubility of NFTs enables their survival after the death of affected nerve cells as extracellular NFTs (or ghost cells) that accumulate in the neuropil (Alzheimer 1907; Braak et al. 1986; Kidd 1963). These extracellular NFTs are probably then engulfed by astrocytes and/or microglial cells where they are presumably slowly degraded. Amyloid plaques consist of aggregates of amyloid peptides (Aβ) which are derived from transmembrane proteins (APP, amyloid precursor protein) as a result of normal proteolysis (Kosik 1992).