Open AccessUpregulated expression of a subset of genes in APP ; ob / ob mice: Evidence of an interaction between diabetes‐linked obesity and Alzheimer’s disease
Author(s) -
Shinohara Mitsuru,
Kikuchi Masataka,
OnishiTakeya Miyuki,
Tashiro Yoshitaka,
Suzuki Kaoru,
Noda Yasuhiro,
Takeda Shuko,
Mukouzono Masahiro,
Nagano Seiichi,
Fukumori Akio,
Morishita Ryuichi,
Nakaya Akihiro,
Sato Naoyuki
Publication year - 2021
Publication title -
faseb bioadvances
Language(s) - English
Resource type - Journals
ISSN - 2573-9832
DOI - 10.1096/fba.2020-00151
Subject(s) - downregulation and upregulation , neurodegeneration , diabetes mellitus , gene , biology , genetically modified mouse , dementia , endocrinology , medicine , disease , transgene , genetics
Clinical studies have indicated that obesity and diabetes are associated with Alzheimer's disease (AD) and neurodegeneration. However, the mechanism by which obesity/diabetes and AD interact with each other and contribute to dementia remains elusive. To obtain insights into their interaction at molecular levels, we performed gene expression analysis of APP ; ob / ob mice, which were generated by crossing transgenic AD model mice (APP23 mice) with ob / ob mice, which are obese and mildly diabetic. The Aβ level in these mice was reduced compared with that in pure APP mice. However, we identified a cluster of genes (cluster 10) upregulated in APP ; ob / ob mice but not in either APP or ob / ob mice. Interestingly, genes upregulated in the human AD brain were enriched in cluster 10. Moreover, genes in cluster 10 formed a network and shared upregulated genes with a cell model of neurodegeneration and other models of neurological disorders such as ischemia and epilepsy. In silico analyses showed that serum response factor (SRF), recently identified in a single‐cell analysis of human brains as a transcription factor that can control the conversion from healthy cells to AD cells, might be a common transcriptional regulator for a subset of cluster 10 genes. These data suggest that upregulation of genes uniquely associated with APP ; ob / ob mice is an evidence of the interaction between obesity/diabetes and AD.