Hypoxia Linked to Progression of Alzheimer Disease
Low oxygen stimulates amyloid-beta processing enzyme
THURSDAY, Nov. 23 (HealthDay News) -- Loss of oxygen flow to the brain may trigger the progression of Alzheimer disease by upregulating a gene that accelerates plaque formation, according to a report published online Nov. 22 in the Proceedings of the National Academy of Sciences Early Edition.
Since having a history of stroke is known to be associated with developing Alzheimer disease, Weihong Song, M.D., Ph.D., of the University of British Columbia in Vancouver, Canada, and colleagues asked whether mimicking the hypoxic conditions caused by stroke affects expression of the amyloid-beta processing enzyme, BACE1 -- a regulator of Alzheimer disease pathogenesis.
Using a gene reporter assay, the investigators identified a hypoxia-responsive element in the promoter of BACE1 and found that hypoxic conditions stimulated both BACE1 expression and amyloid-beta cleavage both in vitro and in vivo. Further, hypoxia increased plaque formation and potentiated memory deficits in mice susceptible to Alzheimer disease.
"Taken together, our results clearly demonstrate that hypoxia can facilitate Alzheimer disease pathogenesis and provide a molecular mechanism linking vascular factors to Alzheimer disease," the authors conclude. "Our study suggests that interventions to improve cerebral perfusion may benefit Alzheimer disease patients."