Increased caveolin-1 expression in Alzheimer's disease brain.
Increasing evidence suggests that cholesterol plays a central role in the pathophysiology of Alzheimer's disease (AD). Caveolin is a cholesterol-binding membrane protein involved in cellular cholesterol transport. We investigated the changes in the protein amount of hippocampal caveolin of autopsy-confirmed AD and aged-matched control subjects. Our results demonstrate that caveolin protein levels in the hippocampus and caveolin mRNA in the frontal cortex are up-regulated in AD by approximately two-fold, compared to control brains. These results suggest a relationship between caveolin-1 expression levels and a dysregulation of cholesterol homeostasis at the plasma membrane of brain cells. In support of this hypothesis, a significant increase in caveolin protein levels has also been observed in hippocampal tissue from ApoE-deficient (knockout) and aged wild-type mice; two situations associated with modifications of transbilayer distribution of cholesterol in brain synaptic plasma membranes. These results indicate that caveolin over-expression is linked to alterations of cholesterol distribution in the plasma membrane of brain cells and are consistent with the notion of a deterioration of cholesterol homeostasis in AD.
Gaudreault
Sophie B
SB
Departments of Psychiatry and Neurology & Neurosurgery, Douglas Hospital Research Centre, McGill University, Montreal, Que., Canada H4A 2B4.
Dea
Doris
D
Poirier
Judes
J
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D016022:Case-Control Studies; D051242:Caveolin 1; D022461:Caveolins / Q000235:genetics / Q000378:metabolism*; D003720:Densitometry / Q000379:methods; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011180:Postmortem Changes; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D001057:Apolipoproteins E; C495540:CAV1 protein, human; C495541:Cav1 protein, mouse; D051242:Caveolin 1; D022461:Caveolins