Altered expression of diabetes-related genes in Alzheimer's disease brains: the Hisayama study.
Bottom Line: Relevant changes in gene expression identified by microarray analysis were validated by quantitative real-time reverse-transcription polymerase chain reaction and western blotting.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.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.
Affiliation: Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Department of Neurosurgery, Graduate School of Medical Sciences.Show MeSH
Related in: MedlinePlus
Mentions: Among the top 200 transcription clusters, 145 genes were eligible for generating IPA networks. The most relevant network included downregulated genes such as MET, PCSK1, PTPN3, SERPINF1, and VEGFA, and upregulated genes such as AEBP1 and TXNIP (Fig. 3A; Network 1). The second-most relevant network consisted of the genes encoding GABA receptors (GABRA1, GABRA4, GABRA5, GABRG2), synaptotagmin members, syntaxin, potassium channels, and regulators of G protein signaling. Expression of all of these genes was markedly decreased in the AD hippocampus (Fig. 3B; Network 2), reflecting the neuronal dysfunction in AD brain. The third-most relevant network consisted of genes regulated by insulin signaling pathways, as discussed below (Fig. 3C; Network 3). The alterations in the expression levels of the genes constituting these 3 networks were well preserved in the temporal cortex and to a lesser extent in the frontal cortex of AD brains (see Supplementary Table S6).Figure 3.
Affiliation: Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Department of Neurosurgery, Graduate School of Medical Sciences.