Affiliations: [a] Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea | [b] Psoma Therapeutics Inc., Seoul, Korea | [c] Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea | [d] Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, Seoul, Korea
Correspondence:
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Correspondence to: Jong-Il Kim, M.D., Ph.D., or Inhee Mook-Jung, Ph.D., Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, 28 Yungun-dong, Jongno-gu, Seoul 110–799, Korea. E-mails: inhee@snu.ac.kr (Inhee Mook-Jung), inhee@snu.ac.kr (Inhee Mook-Jung).
Abstract: The pathogenesis of Alzheimer's disease (AD), especially the early events of AD pathology, remains unknown because of the complexity of AD and limitation of analysis methods. Transcriptome analysis has provided comprehensive insights to investigate the complex cellular activity in brain, but the transcriptome profiles from AD patients with microarray have generated discordant results. Here, for the first time, we performed transcriptome analysis of frontal cortex and cerebellum in 7-week-old 5XFAD transgenic mice (before extracellular amyloid plaque deposits) using high-throughput RNA-Seq analysis. Specific functional annotations were identified with differentially expressed genes (DEGs) of frontal cortex (a typically vulnerable region of AD pathology) and cerebellum (a typically non-vulnerable region of AD pathology). Cardiovascular disease-related genes were significantly found in down-regulated DEGs of frontal cortex, and mitochondrial dysfunction-related genes were evident in down-regulated DEGs of cerebellum. Additionally, we found RNA variants at the nucleotide level in transgenic mice compared with non-transgenic mice. Our results indicate that both frontal cortex and cerebellum in 5XFAD transgenic mice show specific pathological processes in the early pathophysiology of AD.
