Endophilin I Expression Is Increased in the Brains of Alzheimer Disease Patients

Yimin Ren,Hong Wei Xu,Fleur Davey,Margaret Taylor,Jim Aiton,Peter Coote,Fang Fang,Jun Yao,Doris Chen,John Xi Chen,Shi Du Yan,Frank J Gunn-Moore

doi:10.1074/jbc.m707932200

Abstract

Alzheimer patients have increased levels of both the 42 amyloid-beta-peptide (Abeta) and the amyloid binding alcohol dehydrogenase (ABAD), which is an intracellular binding site for Abeta. The overexpression of Abeta and ABAD in transgenic mice has shown that the binding of Abeta 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 Abeta 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.

Highlights

Amyloid-␤ binding alcohol dehydrogenase (ABAD) is a 27-kDa intracellular binding partner for A␤ at nM concentrations [3]
We identified peroxiredoxin II as a protein whose expression increased within the brains isolated from Tg mAPP/ ABAD animals and Alzheimer disease patients
We demonstrate in primary cortical neurons that an increase in endophilin I leads to an increase in Jun N-terminal kinase (JNK) activation with the subsequent death of these neurons

Summary

Introduction

Amyloid-␤ binding alcohol dehydrogenase (ABAD) is a 27-kDa intracellular binding partner for A␤ at nM concentrations [3]. We identified peroxiredoxin II as a protein whose expression increased within the brains isolated from Tg mAPP/ ABAD animals and Alzheimer disease patients. We report the identification of a second protein that is increased within the brains isolated from Tg mAPP/ABAD animals and Alzheimer disease patients.

Results

Conclusion