Endophilin I expression is increased in the brains of Alzheimer disease patients

Abstract

Alzheimer patients have increased levels of both the 42 amyloid-β-peptide (Aβ) and the amyloid binding alcohol dehydrogenase (ABAD), which is an intracellular binding site for Aβ. The overexpression of Aβ and ABAD in transgenic mice has shown that the binding of Aβ to ABAD results in amplified neuronal stress and impairment of learning and memory. From a proteomic analysis of the brains from these animals, we have identified for the first time that the protein endophilin I increases in Alzheimer diseased brain. The increase in endophilin I levels in neurons is linked to an increase in the activation of the stress kinase c-Jun N-terminal kinase with the subsequent death of theneurons. We also demonstrate in living animals that the expression level of endophilin I is an indicator for the interaction of ABAD and Aβ as its expression levels return to normal if this interaction is perturbed. Therefore this identifies endophilin I as a new indicator of the progression of Alzheimer disease. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.