Relationships between expression of apolipoprotein E and beta-amyloid precursor protein are altered in proximity to Alzheimer beta-amyloid plaques: potential explanations from cell culture studies.
Theories regarding the initiation and progression of Alzheimer disease (AD) often consider potential roles played by elevations of beta-amyloid precursor protein (betaAPP). Because it is the source of amyloid beta-peptide, betaAPP may simply contribute more pathogenic stimulus when elevated; some analyses have, however, reported a decline in betaAPP in AD. We found a progressive increase in neuronal betaAPP expression with increasing age in the brains of nondemented individuals, whereas in AD patient samples, betaAPP antigenicity decreased in neuronal somata in a manner that correlated with accumulation of mature amyloid beta-peptide plaques. In contrast, apolipoprotein E (ApoE) expression correlated with accumulation of plaques, and even greater amounts of ApoE were detected in plaques. Induction of betaAPP by glutamate in neuronal cell cultures was found to depend upon ApoE levels or activity. Thus, elevations in expression of ApoE and betaAPP by cellular stresses are likely normally linked in vivo, and uncoupling of this link, or other pathologic events in AD initiation, may leave neurons with diminished betaAPP expression, which might in turn reduce their resistance to stressors.
Barger
Steven W
SW
Department of Geriatrics, Geriatric Research Education and Clinical Center, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA.
DeWall
Kevin Mark
KM
Liu
Ling
L
Mrak
Robert E
RE
Griffin
W Sue T
WS
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001057:Apolipoproteins E / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000166:cytology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D058225:Plaque, Amyloid / Q000473:pathology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats
D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D034741:RNA, Small Interfering; D018698:Glutamic Acid