Swedish mutation within amyloid precursor protein modulates global gene expression towards the pathogenesis of Alzheimer's disease

Jongyeon Shin, Saet Byeol Yu, Un Young Yu, Sangmee Ahn Jo, Jung Hyuck Ahn

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

The Swedish mutation (K595N/M596L) of amyloid precursor protein (APP-swe) has been known to increase abnormal cleavage of cellular APP by Beta-secretase (BACE), which causes tau protein hyperphosphorylation and early-onset Alzheimer's disease (AD). Here, we analyzed the effect of APP-swe in global gene expression using deep transcriptome sequencing technique. We found 283 genes were down-regulated and 348 genes were up-regulated in APP-swe expressing H4-swe cells compared to H4 wild-type cells from a total of approximately 74 million reads of 38 base pairs from each transcriptome. Two independent mechanisms such as kinase and phosphatase signaling cascades leading hyperphosphorylation of tau protein were regulated by the expression of APP-swe. Expressions of catalytic subunit as well as several regulatory subunits of protein phosphatases 2A were decreased. In contrast, expressions of tau-phosphorylating glycogen synthase kinase 3β (GSK-3β), cyclin dependent kinase 5 (CDK5), and cAMP-dependent protein kinase A (PKA) catalytic subunit were increased. Moreover, the expression of AD-related Aquaporin 1 and presenilin 2 expression was regulated by APP-swe. Taken together, we propose that the expression of APP-swe modulates global gene expression directed to AD pathogenesis.

Original languageEnglish
Pages (from-to)704-709
Number of pages6
JournalBMB Reports
Volume43
Issue number10
DOIs
StatePublished - Oct 2010

Keywords

  • Alzheimer's disease
  • Gene expression
  • Swedish mutation
  • Tau protein
  • Transcriptome sequencing

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