Identification of hub genes associated with cognition in the hippocampus of Alzheimer’s Disease

ABSTRACT

Alzheimer’s Disease (AD) is a neurodegenerative disease featured by cognitive impairment. This bioinformatic analysis was used to identify hub genes related to cognitive dysfunction in AD. The gene expression profile GSE48350 in the hippocampus of AD patients aged >70 years was obtained from the Gene Expression Omnibus (GEO) database. A total of 96 differentially expressed genes (DEGs) were identified, and subjected to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses; a protein–protein interaction (PPI) network was constructed. The DEGs were enriched in synapse-related changes. A protein cluster was teased out of PPI. Furthermore, the cognition ranked the first among all the terms of biological process (BP). Next, 4 of 10 hub genes enriched in cognition were identified. The function of these genes was validated using APP/PS1 mice. Cognitive performance was validated by Morris Water Maze (MWM), and gene expression by RT-qPCR, Cholecystokinin (CCK), Tachykinin precursor 1 (TAC1), Calbindin 1 (CALB1) were downregulated in the hippocampus. These genes can provide new directions in the research of the molecular mechanism of AD.

KEYWORDS:

• Alzheimer’s disease
• bioinformatic analysis
• cognition
• GSE48350

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contribution

Study concept and design: Yu-Jia Liu, Tian-Tian Liu Acquisition of data: Yu-Jia Liu, Lin-Hao Jiang Analysis and interpretation: Yu-Jia Liu, Tian-Tian Liu, Qian Liu Critical revision of the manuscript for important intellectual content: Zheng-Liang Ma, Tian-Jiao Xia, Xiao-Ping Gu. Study supervision: Tian-Jiao Xia, Xiao-Ping Gu

Additional information

Funding

This study was supported by the National Natural Science Foundation of China [81701371, 81730033]; the National Key R&D Program of China (GXP, grant numbers 2018YFC2001901); the Natural Science Foundation of Jiangsu Province of China [BK20170654]; and the Key Talents of 13th Five-Year Plan for Strengthening Health of Jiangsu Province [ZDRCA2016069].