Association between methylation of BIN1 promoter in peripheral blood and preclinical Alzheimer's disease.
Association between methylation of BIN1 promoter in peripheral blood and preclinical Alzheimer's disease.
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外周血中 BIN1 启动子甲基化与临床前阿尔茨海默氏病的关联。
DOI：
10.1038/s41398-021-01218-9
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发表时间：
2021-02-02
影响因子：
6.8
通讯作者：
Yu JT
中科院分区：
文献类型：
--
作者：
Hu H;Tan L;Bi YL;Xu W;Tan L;Shen XN;Hou XH;Ma YH;Dong Q;Yu JT
桥接整合子1（BIN 1）基因是继载脂蛋白E（APOE）基因之后的晚发性阿尔茨海默病（LOAD）的第二大易感基因。为了探讨外周血中BIN 1甲基化是否在LOAD早期发生变化，我们从中国阿尔茨海默病生物标志物和生活方式（CABLE）数据库中纳入了814名参与者（484名认知正常参与者[CN]和330名主观认知下降[SCD]）。然后我们检测外周血中BIN 1启动子甲基化与临床前AD易感性或脑脊液（CSF）AD相关生物标志物早期变化的相关性。结果显示，即使在校正协变量后，具有显著AD生物学特征的SCD参与者的BIN 1启动子甲基化水平也较低。BIN 1启动子的低甲基化与所有参与者的CSF Aβ42降低（p = 0.0008）以及p-tau/Aβ42（p = 0.0001）和t-tau/Aβ42（p < 0.0001）增加相关。亚组分析显示，上述相关性仅存在于SCD亚组。此外，在SCD亚组中，BIN 1启动子的低甲基化还伴随CSF p-tau（p = 0.0028）和t-tau（p = 0.0130）增加，这与CSF Aβ42无关。校正单核苷酸多态性位点（SNPs）和APOE β 4状态交互作用后，上述关联仍然显著。我们的研究是第一个发现外周血中BIN 1启动子低甲基化与临床前AD之间存在强相关性的研究。这为BIN 1参与AD提供了新的证据，并可能有助于发现AD的新治疗靶点。
The bridging integrator 1 (BIN1) gene is the second most important susceptibility gene for late-onset Alzheimer’s disease (LOAD) after apolipoprotein E (APOE) gene. To explore whether the BIN1 methylation in peripheral blood changed in the early stage of LOAD, we included 814 participants (484 cognitively normal participants [CN] and 330 participants with subjective cognitive decline [SCD]) from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database. Then we tested associations of methylation of BIN1 promoter in peripheral blood with the susceptibility for preclinical AD or early changes of cerebrospinal fluid (CSF) AD-related biomarkers. Results showed that SCD participants with significant AD biological characteristics had lower methylation levels of BIN1 promoter, even after correcting for covariates. Hypomethylation of BIN1 promoter were associated with decreased CSF Aβ42 (p = 0.0008), as well as increased p-tau/Aβ42 (p = 0.0001) and t-tau/Aβ42 (p < 0.0001) in total participants. Subgroup analysis showed that the above associations only remained in the SCD subgroup. In addition, hypomethylation of BIN1 promoter was also accompanied by increased CSF p-tau (p = 0.0028) and t-tau (p = 0.0130) in the SCD subgroup, which was independent of CSF Aβ42. Finally, above associations were still significant after correcting single nucleotide polymorphic sites (SNPs) and interaction of APOE ɛ4 status. Our study is the first to find a robust association between hypomethylation of BIN1 promoter in peripheral blood and preclinical AD. This provides new evidence for the involvement of BIN1 in AD, and may contribute to the discovery of new therapeutic targets for AD.
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DOI：
10.1016/j.jalz.2011.03.005
发表时间：
2011-05
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
McKhann GM;Knopman DS;Chertkow H;Hyman BT;Jack CR Jr;Kawas CH;Klunk WE;Koroshetz WJ;Manly JJ;Mayeux R;Mohs RC;Morris JC;Rossor MN;Scheltens P;Carrillo MC;Thies B;Weintraub S;Phelps CH
通讯作者：
Phelps CH
影响因子：
9
作者：
Miebach, Lisa;Wolfsgruber, Steffen;Wagner, Michael
通讯作者：
Wagner, Michael
影响因子：
11
作者：
Chapuis, J.;Hansmannel, F.;Gistelinck, M.;Mounier, A.;Van Cauwenberghe, C.;Kolen, K. V.;Geller, F.;Sottejeau, Y.;Harold, D.;Dourlen, P.;Grenier-Boley, B.;Kamatani, Y.;Delepine, B.;Demiautte, F.;Zelenika, D.;Zommer, N.;Hamdane, M.;Bellenguez, C.;Dartigues, J-F;Hauw, J-J;Letronne, F.;Ayral, A-M;Sleegers, K.;Schellens, A.;Broeck, L. V.;Engelborghs, S.;De Deyn, P. P.;Vandenberghe, R.;O'Donovan, M.;Owen, M.;Epelbaum, J.;Mercken, M.;Karran, E.;Bantscheff, M.;Drewes, G.;Joberty, G.;Campion, D.;Octave, J-N;Berr, C.;Lathrop, M.;Callaerts, P.;Mann, D.;Williams, J.;Buee, L.;Dewachter, I.;Van Broeckhoven, C.;Amouyel, P.;Moechars, D.;Dermaut, B.;Lambert, J-C
通讯作者：
Lambert, J-C
影响因子：
25
作者：
De Jager, Philip L.;Srivastava, Gyan;Lunnon, Katie;Burgess, Jeremy;Schalkwyk, Leonard C.;Yu, Lei;Eaton, Matthew L.;Keenan, Brendan T.;Ernst, Jason;McCabe, Cristin;Tang, Anna;Raj, Towfique;Replogle, Joseph;Brodeur, Wendy;Gabriel, Stacey;Chai, High S.;Younkin, Curtis;Younkin, Steven G.;Zou, Fanggeng;Szyf, Moshe;Epstein, Charles B.;Schneider, Julie A.;Bernstein, Bradley E.;Meissner, Alex;Ertekin-Taner, Nilufer;Chibnik, Lori B.;Kellis, Manolis;Mill, Jonathan;Bennett, David A.
通讯作者：
Bennett, David A.
DOI：
10.1093/gerona/52a.2.m117
发表时间：
1997-03-01
影响因子：
5.1
作者：
Gatz, M;Pedersen, NL;Ahlbom, A
通讯作者：
Ahlbom, A