Variants in triggering receptor expressed on myeloid cells 2 are associated with both behavioral variant frontotemporal lobar degeneration and Alzheimer's disease.
Variants in triggering receptor expressed on myeloid cells 2 are associated with both behavioral variant frontotemporal lobar degeneration and Alzheimer's disease.
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DOI：
10.1016/j.neurobiolaging.2013.02.016
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发表时间：
2013-08
影响因子：
4.2
通讯作者：
Huentelman MJ
中科院分区：
文献类型：
--
作者：
Giraldo M;Lopera F;Siniard AL;Corneveaux JJ;Schrauwen I;Carvajal J;Muñoz C;Ramirez-Restrepo M;Gaiteri C;Myers AJ;Caselli RJ;Kosik KS;Reiman EM;Huentelman MJ
最近的证据表明，TREM2基因中罕见的遗传变异与阿尔茨海默病风险的增加有关。TREM2突变是以多囊脂肪膜性骨发育不良伴硬化性白质脑病(PLOSL)和早发性痴呆综合征为特征的疾病的遗传基础。TREM2在脑内小胶质细胞吞噬凋亡神经细胞的过程中起重要作用。功能丧失可能会导致坏死性碎片的清除和堆积受损，进而导致神经变性。在这项研究中，我们调查了哥伦比亚安提奥基亚的一个分离常染色体隐性行为变异FTLD的血缘家庭。外显子组测序发现TREM2(p.Trp198X)有一个无义突变，与疾病分离。接下来，使用一组临床特征和神经病理学证实的散发性AD病例和对照，我们报告了在TREM2中的rs75932628处AD风险关联的复制。这些数据表明，TREM2的突变负担可能是神经退行性疾病的危险因素，潜在地，这类患有痴呆症的TREM2变异携带者应该被认为是一种分子上不同的神经退行性疾病。
Recent evidence suggests that rare genetic variants within the TREM2 gene are associated with increased risk for Alzheimer’s disease. TREM2 mutations are the genetic basis for a condition characterized by polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) and an early-onset dementia syndrome. TREM2 is important in the phagocytosis of apoptotic neuronal cells by microglia in the brain. Loss of function might lead to an impaired clearance and accumulation of necrotic debris and subsequent neurodegeneration. In this study, we investigated a consanguineous family segregating autosomal recessive behavioral variant FTLD from Antioquia, Colombia. Exome sequencing identified a nonsense mutation in TREM2 (p.Trp198X) segregating with disease. Next, using a cohort of clinically characterized and neuropathologically verified sporadic AD cases and controls we report replication of the AD risk association at rs75932628 within TREM2. These data suggest that mutational burden in TREM2 may serve as a risk factor for neurodegenerative disease in general and that potentially this class of TREM2 variant carriers with dementia should be considered a molecularly distinct form of neurodegenerative disease.
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DOI：
10.4049/jimmunol.1102836
发表时间：
2012-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Otero K;Shinohara M;Zhao H;Cella M;Gilfillan S;Colucci A;Faccio R;Ross FP;Teitelbaum SL;Takayanagi H;Colonna M
通讯作者：
Colonna M
DOI：
10.1056/nejmoa1211851
发表时间：
2013-01-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Guerreiro R;Wojtas A;Bras J;Carrasquillo M;Rogaeva E;Majounie E;Cruchaga C;Sassi C;Kauwe JS;Younkin S;Hazrati L;Collinge J;Pocock J;Lashley T;Williams J;Lambert JC;Amouyel P;Goate A;Rademakers R;Morgan K;Powell J;St George-Hyslop P;Singleton A;Hardy J;Alzheimer Genetic Analysis Group
通讯作者：
Alzheimer Genetic Analysis Group
影响因子：
3.5
作者：
Corneveaux, Jason J.;Myers, Amanda J.;Huentelman, Matthew J.
通讯作者：
Huentelman, Matthew J.
影响因子：
5.3
作者：
Carvajal-Carmona, LG;Ophoff, R;Ruiz-Linares, A
通讯作者：
Ruiz-Linares, A
影响因子：
4
作者：
Bianchin, MM;Capella, HM;Sakamoto, AC
通讯作者：
Sakamoto, AC