Effect of complement CR1 on brain amyloid burden during aging and its modification by APOE genotype.
Effect of complement CR1 on brain amyloid burden during aging and its modification by APOE genotype.
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DOI：
10.1016/j.biopsych.2012.08.015
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发表时间：
2013-03-01
影响因子：
10.6
通讯作者：
Resnick, Susan M.
中科院分区：
文献类型：
--
作者：
Thambisetty, Madhav;An, Yang;Nalls, Michael;Sojkova, Jitka;Swaminathan, Shanker;Zhou, Yun;Singleton, Andrew B.;Wong, Dean F.;Ferrucci, Luigi;Saykin, Andrew J.;Resnick, Susan M.
CR1中的rs3818361单核苷酸多态性与阿尔茨海默病（AD）的风险增加相关。虽然这种新的变异与一个小的效应大小，是不太可能是有用的AD风险的预测，它可能提供深入了解AD的发病机制。我们研究了rs3818361与非痴呆老年人脑淀粉样蛋白沉积之间的关系。在巴尔的摩老龄化纵向研究的神经影像子研究中，我们使用11 C-匹兹堡化合物-B（PiB）PET对57名非痴呆老年人（平均年龄78.5岁）的脑淀粉样蛋白负荷进行定量。在一项重复研究中，我们分析了阿尔茨海默病神经影像学倡议（ADNI）数据集中22名认知正常老年人（平均年龄77.1岁）的11C-PiB PET数据。rs3818361危险等位基因携带者相对于非携带者具有较低的脑淀粉样蛋白负荷。与高危携带者相比，非携带者脑淀粉样蛋白沉积的变异性明显更大，APOE基因型可以部分解释这种效应。在CR1危险等位基因的非携带者中，APOE ε 4个体相对于APOE ε 4非携带者显示出显著更高的脑淀粉样蛋白负荷。我们还独立地重复了我们在ADNI样本中rs3818361风险等位基因携带者中脑淀粉样蛋白负荷较低的观察结果。我们的研究结果表明，在AD中CR1，APOE和脑淀粉样蛋白通路相互作用的复杂机制。我们的研究结果与针对有AD风险的非痴呆个体的脑A β的治疗相关，并表明此类治疗的临床结果可能受到复杂的基因-基因相互作用的影响。
The rs3818361 single nucleotide polymorphism in CR1 is associated with increased risk of Alzheimer's disease (AD). Although this novel variant is associated with a small effect size and, is unlikely to be useful as a predictor of AD risk, it may provide insights into AD pathogenesis. We examined the association between rs3818361 and brain amyloid deposition in non-demented older individuals. We used 11C-Pittsburgh Compound-B (PiB) PET to quantify brain amyloid burden in 57 non-demented older individuals (mean age 78.5 years) in the neuroimaging substudy of the Baltimore Longitudinal Study of Aging. In a replication study, we analyzed 11C-PiB PET data from 22 cognitively normal older individuals (mean age 77.1 years) in the Alzheimer's disease neuroimaging initiative (ADNI) dataset. Risk allele carriers of rs3818361 have lower brain amyloid burden relative to non-carriers. There is a strikingly greater variability in brain amyloid deposition in the non-carrier group relative to risk carriers, an effect explained partly by APOE genotype. In non-carriers of the CR1 risk allele, APOE ε4 individuals showed significantly higher brain amyloid burden relative to APOE ε4 non-carriers. We also independently replicate our observation of lower brain amyloid burden in risk allele carriers of rs3818361 in the ADNI sample. Our findings suggest complex mechanisms underlying the interaction of CR1, APOE and brain amyloid pathways in AD. Our results are relevant to treatments targeting brain Aβ in non-demented individuals at risk for AD and suggest that clinical outcomes of such treatments may be influenced by complex gene-gene interactions.
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影响因子：
2.2
作者：
Reiman EM;Langbaum JB;Tariot PN
通讯作者：
Tariot PN
影响因子：
30.8
作者：
Harold, Denise;Abraham, Richard;Hollingworth, Paul;Sims, Rebecca;Gerrish, Amy;Hamshere, Marian L.;Pahwa, Jaspreet Singh;Moskvina, Valentina;Dowzell, Kimberley;Williams, Amy;Jones, Nicola;Thomas, Charlene;Stretton, Alexandra;Morgan, Angharad R.;Lovestone, Simon;Powell, John;Proitsi, Petroula;Lupton, Michelle K.;Brayne, Carol;Rubinsztein, David C.;Gill, Michael;Lawlor, Brian;Lynch, Aoibhinn;Morgan, Kevin;Brown, Kristelle S.;Passmore, Peter A.;Craig, David;McGuinness, Bernadette;Todd, Stephen;Holmes, Clive;Mann, David;Smith, A. David;Love, Seth;Kehoe, Patrick G.;Hardy, John;Mead, Simon;Fox, Nick;Rossor, Martin;Collinge, John;Maier, Wolfgang;Jessen, Frank;Schuermann, Britta;van den Bussche, Hendrik;Heuser, Isabella;Kornhuber, Johannes;Wiltfang, Jens;Dichgans, Martin;Froelich, Lutz;Hampel, Harald;Huell, Michael;Rujescu, Dan;Goate, Alison M.;Kauwe, John S. K.;Cruchaga, Carlos;Nowotny, Petra;Morris, John C.;Mayo, Kevin;Sleegers, Kristel;Bettens, Karolien;Engelborghs, Sebastiaan;De Deyn, Peter P.;Van Broeckhoven, Christine;Livingston, Gill;Bass, Nicholas J.;Gurling, Hugh;McQuillin, Andrew;Gwilliam, Rhian;Deloukas, Panagiotis;Al-Chalabi, Ammar;Shaw, Christopher E.;Tsolaki, Magda;Singleton, Andrew B.;Guerreiro, Rita;Muehleisen, Thomas W.;Noethen, Markus M.;Moebus, Susanne;Joeckel, Karl-Heinz;Klopp, Norman;Wichmann, H-Erich;Carrasquillo, Minerva M.;Pankratz, V. Shane;Younkin, Steven G.;Holmans, Peter A.;O'Donovan, Michael;Owen, Michael J.;Williams, Julie
通讯作者：
Williams, Julie
影响因子：
11.2
作者：
Chibnik, Lori B.;Shulman, Joshua M.;Leurgans, Sue E.;Schneider, Julie A.;Wilson, Robert S.;Tran, Dong;Aubin, Cristin;Buchman, Aron S.;Heward, Christopher B.;Myers, Amanda J.;Hardy, John A.;Huentelman, Matthew J.;Corneveaux, Jason J.;Reiman, Eric M.;Evans, Denis A.;Bennett, David A.;De Jager, Philip L.
通讯作者：
De Jager, Philip L.
DOI：
10.3233/jad-2011-101932
发表时间：
2011
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Carrasquillo MM;Belbin O;Hunter TA;Ma L;Bisceglio GD;Zou F;Crook JE;Pankratz VS;Sando SB;Aasly JO;Barcikowska M;Wszolek ZK;Dickson DW;Graff-Radford NR;Petersen RC;Morgan K;Younkin SG
通讯作者：
Younkin SG
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y