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.
Pluta
R
R
Department of Neuropathology, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland. rp@ibbrain.ibb.waw.pl
D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000503:physiopathology*; D009410:Nerve Degeneration; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D013997:Time Factors
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E