Expression of heat shock proteins in Alzheimer's disease.
In an investigation of heat shock proteins (HSPs) in the brains of Alzheimer's disease (AD) patients and cognitively intact control subjects, we found that 2 HSPs, termed "HSP72" and "GRP78," underwent major changes in expression in AD. HSP72, which was present at very low levels in control brains, increased dramatically in AD patients, and was localized exclusively in neuritic plaques and neurofibrillary tangles. We hypothesize that HSP72 is induced as an early response to the formation of abnormal proteins, perhaps targeting them for proteolysis. In contrast, GRP78 increased in AD only in neurons that remained cytologically normal, especially in the CA3 subfield of the hippocampus and the deep layers of the entorhinal cortex. The increased expression of GRP78 within successfully surviving neurons suggests that this protein may protect such cells from AD-specific damage.
Hamos
J E
JE
Department of Neurology, University of Massachusetts Medical Center, Worcester 01655.
Oblas
B
B
Pulaski-Salo
D
D
Welch
W J
WJ
Bole
D G
DG
Drachman
D A
DA
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D003720:Densitometry; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008032:Limbic System / Q000378:metabolism; D008875:Middle Aged; D018832:Molecular Chaperones; D012016:Reference Values
D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones