Altered expression of diabetes-related genes in Alzheimer's disease brains: The Hisayama study

Masaaki Hokama, Sugako Oka, Julio Leon, Toshiharu Ninomiya, Hiroyuki Honda, Kensuke Sasaki, Toru Iwaki, Tomoyuki Ohara, Tomio Sasaki, Frank M. LaFerla, Yutaka Kiyohara, Yusaku Nakabeppu

Research output: Contribution to journalArticlepeer-review

157 Citations (Scopus)

Abstract

Diabetes mellitus (DM) is considered to be a risk factor for dementia including Alzheimer's disease (AD). However, the molecular mechanism underlying this risk is not well understood. We examined gene expression profiles in postmortem human brains donated for the Hisayama study. Three-way analysis of variance of microarray data from frontal cortex, temporal cortex, and hippocampus was performed with the presence/absence of AD and vascular dementia, and sex, as factors. Comparative analyses of expression changes in the brains of AD patients and a mouse model of AD were also performed. Relevant changes in gene expression identified by microarray analysis were validated by quantitative real-time reverse-transcription polymerase chain reaction and western blotting. The hippocampi of AD brains showed the most significant alteration in gene expression profile. Genes involved in noninsulin-dependent DM and obesity were significantly altered in both AD brains and the AD mouse model, as were genes related to psychiatric disorders and AD. The alterations in the expression profiles of DM-related genes in AD brains were independent of peripheral DM-related abnormalities. These results indicate that altered expression of genes related to DM in AD brains is a result of AD pathology, which may thereby be exacerbated by peripheral insulin resistance or DM.

Original languageEnglish
Pages (from-to)2476-2488
Number of pages13
JournalCerebral Cortex
Volume24
Issue number9
DOIs
Publication statusPublished - Sep 2014

All Science Journal Classification (ASJC) codes

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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