Increased APOE ε4 expression is associated with the difference in Alzheimer's disease risk from diverse ancestral backgrounds.
Increased APOE ε4 expression is associated with the difference in Alzheimer's disease risk from diverse ancestral backgrounds.
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DOI：
10.1002/alz.12287
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发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
Vance JM
中科院分区：
文献类型：
--
作者：
Griswold AJ;Celis K;Bussies PL;Rajabli F;Whitehead PL;Hamilton-Nelson KL;Beecham GW;Dykxhoorn DM;Nuytemans K;Wang L;Gardner OK;Dorfsman DA;Bigio EH;Mesulam MM;Weintraub S;Geula C;Gearing M;McGrath-Martinez E;Dalgard CL;Scott WK;Haines JL;Pericak-Vance MA;Young JI;Vance JM
APOEε4 confers less risk for Alzheimer disease (AD) in carriers with African local genomic ancestry (ALA) than APOEε4 carriers with European local ancestry (ELA). Cell type specific transcriptional variation between the two local ancestries (LAs) could contribute to this disease risk differences. Single-nucleus RNA sequencing was performed on frozen frontal cortex of homozygous APOEε4 AD patients: seven with ELA, four with ALA. 60,908 nuclei were sequenced. Within the LA region (chr19:44–46Mb), APOEε4 was the gene most differentially expressed, with ELA carriers having significantly more expression (overall p < 1.8E−317) in 24 of 32 cell clusters. The transcriptome of one astrocyte cluster, with high APOEε4 expression and specific to ELA, is suggestive of A1 reactive astrocytes. AD patients with ELA expressed significantly greater levels of APOE than ALA APOEε4 carriers. These differences in APOEε4 expression could contribute to the reduced risk for AD seen in African APOEε4 carriers.
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
2.7
作者：
Kikuchi, Masataka;Hara, Norikazu;Nakaya, Akihiro
通讯作者：
Nakaya, Akihiro
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
--
DOI：
10.3233/jad-142772
发表时间：
2015
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
O'Day DH;Eshak K;Myre MA
通讯作者：
Myre MA
影响因子：
3.5
作者：
Bray, NJ;Jehu, L;O'Donovan, MC
通讯作者：
O'Donovan, MC