THE ROLE OF A-BETA-42 IN ALZHEIMERS-DISEASE

Our recent studies of plasma, fibroblasts, transfected cells and trans genic mice show that a fundamental effect of the mutations linked to f amilial Alzheimer's disease (FAD) is to increase the extracellular con centration of A beta 42. This effect of the FAD-linked mutations is li kely to be directly related to the pathogenesis of Alzheimer's disease (AD) because A beta 42 is deposited early and selectively in the seni le plaques that are an invariant feature of all forms of AD. Thus our results provide strong evidence that the FAD-linked mutations all caus e AD by increasing the extracellular concentration of A beta 42 (43), thereby fostering A beta deposition, and they support the hypothesis t hat cerebral A beta deposition is an essential early event ir. the pat hogenesis of all forms of AD. Interactions between the basal forebrain cholinergic system and A beta that could influence AD pathogenesis ar e discussed. ((C)Elsevier, Paris).