The role of A beta 42 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 A beta 42. This effect of the FAD-linked mutations is likely to be directly related to the pathogenesis of Alzheimer's disease (AD) because A beta 42 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 A beta 42 (43), thereby fostering A beta deposition, and they support the hypothesis that cerebral A beta deposition is an essential early event in the pathogenesis of all forms of AD. Interactions between the basal forebrain cholinergic system and A beta that could influence AD pathogenesis are discussed.
Younkin
S G
SG
Mayo Clinic Jacksonville, Florida 32224, USA.
D017668:Age of Onset; D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D002986:Clinical Trials as Topic; D006801:Humans; D009154:Mutation; D010446:Peptide Fragments / Q000502:physiology*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)