The role of Aβ42 in Alzheimer's disease

Our recent studies of plasma, fibroblasts, transfected cells and transgenic mice show that a fundamental effect of the mutations linked to familial Alzheimer's disease (FAD) is to increase the extracellular concentration of Aβ42. This effect of the FAD-linked mutations is likely to be directly related to the pathogenesis of Alzheimer's disease (AD) because Aβ42 is deposited early and selectively in the senile plaques that are an invariant feature of all forms of AD. Thus our results provide strong evidence that the FAD-linked mutations all cause AD by increasing the extracellular concentration of Aβ42 (43), thereby fostering Aβ deposition, and they support the hypothesis that cerebral Aβ deposition is an essential early event in the pathogenesis of all forms of AD. Interactions between the basal forebrain cholinergic system and Aβ that could influence AD pathogenesis are discussed.