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Impaired energy metabolism linked with initiation of plaques in Alzheimer's brain
Date:12/24/2008

IF2? increased BACE1 levels and enhanced Aβ production while inhibition of eIF2? phosphorylation prevented energy-deprivation induced increases in BACE1.

The researchers went on to show that energy inhibition increased eIF2? phosphorylation, BACE1 levels and amyloid plaque formation in APP transgenic mice. In addition, phosphorylated eIF2? and BACE1 were elevated in an aggressive A? plaque-forming mouse model and in humans with AD.

"Here, for the first time we provide evidence linking impaired energy metabolism, an AD-relevant stress, with BACE1 translation mediated by eIF2? phosphorylation," says Dr. Vassar. "Our findings implicate phosphorylated eIF2? in both the initiation and progression of sporadic AD. Future experiments will determine whether inhibition of eIF2? phosphorylation could be an efficacious therapeutic approach for the prevention and treatment of AD."


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Contact: Cathleen Genova
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