IONIC EFFECTS OF THE ALZHEIMERS-DISEASE BETA-AMYLOID PRECURSOR PROTEIN AND ITS METABOLIC FRAGMENTS

Alzheimer's disease is a progressive dementia characterized in part by deposition of proteinaceous plaques in various areas of the brain. Th e main plaque protein component is beta-amyloid, a metabolic product o f the beta-amyloid precursor protein. Substantial evidence has implica ted beta-amyloid (and other amyloidogenic fragments of the precursor p rotein) with the neurodegeneration observed in Alzheimer's disease. Re cently, beta-amyloid precursor protein and its amyloidogenic metabolic fragments have been shown to alter cellular ionic activity, either th rough interaction with existing channels or by de novo channel formati on. Such alteration in ionic homeostasis has also been linked with cel lular toxicity and might provide a molecular mechanism underlying the neurodegeneration seen in Alzheimer's disease.