Title

Regional selectivity of rab5 and rab7 protein upregulation in mild cognitive impairment and Alzheimer's disease

Document Type

Article

Abstract

Endocytic alterations are one of the earliest changes to occur in Alzheimer's disease (AD), and are hypothesized to be involved in the selective vulnerability of specific neuronal populations during the progression of AD. Previous microarray and real-time quantitative PCR experiments revealed an upregulation of the early endosomal effector rab5 and the late endosome constituent rab7 in the hippocampus of people with mild cognitive impairment (MCI) and AD. To assess whether these select rab GTPase gene expression changes are reflected in protein levels within selectively vulnerable brain regions (basal forebrain, frontal cortex, and hippocampus) and relatively spared areas (cerebellum and striatum), we performed immunoblot analysis using antibodies directed against rab5 and rab7 on postmortem human brain tissue harvested from cases with a premortem clinical diagnosis of no cognitive impairment (NCI), MCI, and AD. Results indicate selective upregulation of both rab5 and rab7 levels within basal forebrain, frontal cortex, and hippocampus in MCI and AD, which also correlated with Braak staging. In contrast, no differences in protein levels were found in the less vulnerable cerebellum and striatum. These regional immunoblot assays are consistent with single cell gene expression data, and provide protein-based evidence for endosomal markers contributing to the vulnerability of cell types within selective brain regions during the progression of AD.

Medical Subject Headings

Aged; Aged, 80 and over; Alzheimer Disease (metabolism, pathology, physiopathology); Brain (metabolism, pathology); Cognition Disorders (metabolism, pathology, physiopathology); Female; Humans; Male; Up-Regulation (physiology); rab GTP-Binding Proteins (metabolism); rab5 GTP-Binding Proteins (metabolism); rab7 GTP-Binding Proteins

Publication Date

1-1-2010

Publication Title

Journal of Alzheimer's disease : JAD

E-ISSN

1875-8908

Volume

22

Issue

2

First Page

631

Last Page

9

PubMed ID

20847427

Digital Object Identifier (DOI)

10.3233/JAD-2010-101080

This document is currently not available here.

Share

COinS