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

Stephen D. Ginsberg, Elliott J. Mufson, Scott E. Counts, Joanne Wuu, Melissa J. Alldred, Ralph A. Nixon, Shaoli Che

Research output: Contribution to journalArticle

69 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)631-639
Number of pages9
JournalJournal of Alzheimer's Disease
Volume22
Issue number2
DOIs
StatePublished - 2010

Keywords

  • Basal forebrain
  • cerebellum
  • endosome
  • frontal cortex
  • hippocampus
  • mild cognitive impairment
  • rab GTPase
  • selective vulnerability
  • striatum

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

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