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공공누리This item is licensed Korea Open Government License

Title
Brain somatic mutations observed in Alzheimer’s disease associated with aging and dysregulation of tau phosphorylation
Author(s)
이준학유석종묵인희이정호김일빈정은선김상우김명희손현주박영목김상현박준성
Publisher
Springer Nature
Publication Year
2019-07-12
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.
Journal Title
Nature Communications;
Citation Volume
10
ISSN
2041-1723
DOI
10.1038/s41467-019-11000-7
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Appears in Collections:
7. KISTI 연구성과 > 학술지 발표논문
URI
https://repository.kisti.re.kr/handle/10580/16071
Fulltext
 https://scienceon.kisti.re.kr/srch/selectPORSrchArticle.do?cn=NART99938061
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