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

Alzheimer patients have increased levels of both the 42 amyloid-beta-peptide(A beta) and the amyloid binding alcohol dehydrogenase (ABAD), which is an intracellular binding site for A beta. The overexpression of A beta and ABAD in transgenic mice has shown that the binding of A beta 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 the neurons. We also demonstrate in living animals that the expression level of endophilin I is an indicator for the interaction of ABAD and A beta 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.