Chapter 16 Molecular pathology of head trauma: altered βAPP metabolism and the aetiology of Alzheimer's disease

Abstract

Publisher Summary Considerable progress has been made in determining the identity of the proteins and molecular events involved in the molecular pathology of Alzheimer's disease (AD), the most widely known of which are the inevitability of Alzheimer's disease in Downs syndrome patients with trisomy of chromosome 21 and the point mutations at codon 717 within exon 17 of the β -amyloid precursor protein gene on chromosome 21. However, these genetic causes of Alzheimer's disease account for a vanishingly small proportion of patients who suffer from the disease. It is probable that the overwhelming majority of cases are caused by a variety of environmental factors, which may be either sufficient to trigger disease by themselves or sufficient when acting synergistically with the patients genotype. One of the best-documented environmental precipitants of Alzheimer's disease is a previous history of head trauma. AD can be caused by a variety of factors. Approximately 20% of AD cases are thought to be familial with almost 5% exhibiting an autosomal dominant pattern of inheritanc. Screening of the amyloid precursor protein ( β APP) gene on chromosome 21, which gives rise to the β -amyloid protein found in plaques, has revealed a mutation in some AD families.