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공공누리This item is licensed Korea Open Government License

dc.contributor.author
이준학
dc.contributor.author
유석종
dc.contributor.author
묵인희
dc.contributor.author
이정호
dc.contributor.author
김일빈
dc.contributor.author
정은선
dc.contributor.author
김상우
dc.contributor.author
김명희
dc.contributor.author
손현주
dc.contributor.author
박영목
dc.contributor.author
김상현
dc.contributor.author
박준성
dc.date.accessioned
2021-09-14T06:26:16Z
dc.date.available
2021-09-14T06:26:16Z
dc.date.issued
2019-07-12
dc.identifier.issn
2041-1723
dc.identifier.uri
https://repository.kisti.re.kr/handle/10580/16071
dc.description.abstract
The role of brain somatic mutations in Alzheimer’s disease (AD) is not well understood. Here, we perform deep whole-exome sequencing (average read depth 584×) in 111 postmortem hippocampal formation and matched blood samples from 52 patients with AD and 11 individuals not affected by AD. The number of somatic single nucleotide variations (SNVs) in AD brain specimens increases significantly with aging, and the rate of mutation accumulation in the brain is 4.8-fold slower than that in AD blood. The putatively pathogenic brain somatic mutations identified in 26.9% (14 of 52) of AD individuals are enriched in PI3K-AKT, MAPK, and AMPK pathway genes known to contribute to hyperphosphorylation of tau. We show that a pathogenic brain somatic mutation in PIN1 leads to a loss-of-function mutation. In vitro mimicking of haploinsufficiency of PIN1 aberrantly increases tau phosphorylation and aggregation. This study provides new insights into the genetic architecture underlying the pathogenesis of AD.
dc.language.iso
eng
dc.publisher
Springer Nature
dc.relation.ispartofseries
Nature Communications;
dc.title
Brain somatic mutations observed in Alzheimer’s disease associated with aging and dysregulation of tau phosphorylation
dc.identifier.doi
10.1038/s41467-019-11000-7
dc.citation.number
1
dc.citation.startPage
3090
dc.citation.volume
10
dc.contributor.approver
KOAR, ADMIN
dc.date.dateaccepted
2021-09-14T06:26:16Z
dc.date.datesubmitted
2021-09-14T06:26:16Z
dc.identifier.bibliographicCitation
vol. 10, no. 1, page. 3090
dc.identifier.url
https://scienceon.kisti.re.kr/srch/selectPORSrchArticle.do?cn=NART99938061
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7. KISTI 연구성과 > 학술지 발표논문
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