A human carboxypeptidase E/NF-α1 gene mutation in an Alzheimer's disease patient leads to dementia and depression in mice.

ABSTRACT: Patients with Alzheimer's disease (AD), a common dementia among the aging population, often also suffer from depression. This comorbidity is poorly understood. Although most forms of AD are not genetically inherited, we have identified a new human mutation in the carboxypeptidase E (CPE)/neurotrophic factor-α1 (NF-α1) gene from an AD patient that caused memory deficit and depressive-like behavior in transgenic mice. This mutation consists of three adenosine inserts, introducing nine amino acids, including two glutamines into the mutant protein, herein called CPE-QQ. Expression of CPE-QQ in Neuro2a cells demonstrated that it was not secreted, but accumulated in the endoplasmic reticulum and was subsequently degraded by proteasomes. Expression of CPE-QQ in rat hippocampal neurons resulted in

SUBMITTER: Cheng Y 

PROVIDER: S-EPMC5315563 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature