Alzheimer's disease: β-Amyloid protein and tau

✍ Scribed by Maho Morishima-Kawashima; Yasuo Ihara

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 182 KB
• Volume: 70
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.10355

✦ Synopsis

Abstract

Research on the molecular pathogenesis of Alzheimer's disease (AD) has made great strides over the last decade. This progress is the result of protein chemical analysis of two extracellular and intracellular fibrillary lesions in AD brain conducted during the 1980s, which identified β‐amyloid protein (Aβ) and tau as their major components, respectively. Linkage analysis of familial AD identified four responsible genes: three causative genes (β‐amyloid precursor protein, presenilin 1, and presenilin 2) and one susceptibility gene (apolipoprotein E ϵ__4__). All those genes causing and predisposing to AD exhibit a common phenotype: an increased production of Aβ42, a longer, more amyloidogenic Aβ species, and/or its enhanced deposition. This observation was substantiated when presenilins were shown to be directly involved in Aβ production. Whereas Aβ deposition is relatively specific for AD, tau deposition is observed in various neurodegenerative diseases and is assumed to be intimately associated with neuronal loss. The genetic analysis of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP‐17) revealed the presence of mutations in the tau gene in affected members. Thus, tau can lead to intracellular tau deposits and neuronal loss, although the mechanism remains to be clarified. Taken together, Aβ might exert neurotoxicity through tau, leading to neuronal loss in the AD brain. © 2002 Wiley‐Liss, Inc.