title: RNA-Seq analysis of frontal cortex and cerebellum from 5XFAD mice at early stage of disease pathology.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Kyung Hwa
authors.initials: KH
authors.lastname: Kim
authors.forename: Minho
authors.initials: M
authors.lastname: Moon
authors.forename: Saet-Byeol
authors.initials: SB
authors.lastname: Yu
authors.forename: Inhee
authors.initials: I
authors.lastname: Mook-Jung
authors.forename: Jong-Il
authors.initials: JI
authors.lastname: Kim
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D002318:Cardiovascular Diseases / Q000235:genetics; D002531:Cerebellum / Q000378:metabolism*; D004195:Disease Models, Animal; D005625:Frontal Lobe / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000235:genetics*; D053263:Gene Regulatory Networks; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics; D017423:Sequence Analysis, RNA / Q000379:methods*; D059467:Transcriptome
chemical_list: D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1