ALTERED PROCESSING OF ALZHEIMER AMYLOID PRECURSOR PROTEIN IN RESPONSETO NEURONAL DEGENERATION

In the brains of individuals with Alzheimer disease, senile plaques co ntaining aggregates of beta-amyloid peptide, derived from the beta-amy loid precursor protein (APP), are seen in association with degeneratin g nerve terminals. It is not known whether the degenerating nerve term inals cause the formation of these aggregates or whether beta-amyloid peptide in the aggregates causes nerve-terminal degeneration. In the p resent study of rat brain, degeneration either of local neurons or of nerve terminals caused decreased levels of a neuron-enriched isoform o f APP, increased levels of a glia-enriched isoform of APP, and increas ed levels of potentially amyloidogenic, as well as nonamyloidogenic, C OOH-terminal fragments of APP. Our results demonstrate that neuronal d egeneration affects APP processing and suggest that it may contribute to amyloid formation in mammalian brain.