title: Altered expression of diabetes-related genes in Alzheimer's disease brains: the Hisayama study.
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.
authors.affiliation: Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Department of Neurosurgery, Graduate School of Medical Sciences.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Hokama
authors.affiliation: Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Research Center for Nucleotide Pool.
authors.forename: Sugako
authors.initials: S
authors.lastname: Oka
authors.affiliation: Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation.
authors.forename: Julio
authors.initials: J
authors.lastname: Leon
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ninomiya
authors.affiliation: Department of Neuropathology, Graduate School of Medical Sciences.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Honda
authors.affiliation: Department of Neuropathology, Graduate School of Medical Sciences.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Neuropathology, Graduate School of Medical Sciences.
authors.forename: Toru
authors.initials: T
authors.lastname: Iwaki
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medical Sciences.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ohara
authors.affiliation: Department of Neurosurgery, Graduate School of Medical Sciences.
authors.forename: Tomio
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, CA 92697, USA.
authors.forename: Frank M
authors.initials: FM
authors.lastname: LaFerla
authors.affiliation: Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan and.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kiyohara
authors.affiliation: Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Research Center for Nucleotide Pool.
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Nakabeppu
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D015140:Dementia, Vascular / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D008822:Mice, Transgenic; D013702:Temporal Lobe / Q000378:metabolism*
keywords: animal model; hippocampus; insulin; microarray; postmortem brains