The role of apolipoprotein E in the deposition of beta-amyloid peptide during ischemia-reperfusion brain injury. A model of early Alzheimer's disease.

Transient brain ischemia in the rat produces a stereotyped pattern of selective neuronal degeneration which simulates early Alzheimer's disease (AD) pathology. The aim of the present study was to determine if apolipoprotein E (ApoE) variables are related to alterations in other proteins which play a central role in the pathogenesis of AD; amyloid precursor protein (APP) and beta-amyloid peptide (A beta). The postischemic time course of ApoE and APP and A beta immunoreactivity in brain was examined at survival time from 2 days to 1 year in rats subjected to 10 min cardiac arrest. These data indicate that there are long lasting alterations of ApoE and A beta after brain ischemia. The most likely stimulus for promoting increase of both ApoE and A beta expression are ischemic-reperfusion processes. Our data suggest that ApoE modulates the outcome following cerebral ischemia via molecular events in common with AD pathogenesis. We propose that ischemic-reperfusion processes in brain are the fountain-head of a cycle of molecular and cellular events that have neurodegenerative consequences which finally lead to AD.