TREM2 risk variants are associated with atypical Alzheimer's disease.
TREM2 risk variants are associated with atypical Alzheimer's disease.
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DOI：
10.1007/s00401-022-02495-4
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发表时间：
2022-12
影响因子：
12.7
通讯作者：
中科院分区：
文献类型：
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作者：
阿尔茨海默氏病（AD）具有多种临床和病理学定义的亚型，其中这种异质性的根本原因还没有很好地建立。除了其他神经退行性疾病临床表型外，罕见的TREM2变体还可显著增加临床AD的风险。TREM2变体是否与AD的非典型临床或病理学定义的亚型相关尚不清楚。我们在这里研究了尸检证实的队列中与TREM2风险变体相关的临床和病理特征。TREM2变异病例更常与非遗忘性临床综合征相关。病理学上，TREM2变异病例与神经元缠结密度的非典型分布相关，海马NFT负荷相对于新皮质NFT蓄积显著降低。此外，NFT密度而非淀粉样蛋白负荷与营养不良性小胶质细胞的增加相关。TREM2变异病例与共病的患病率、程度或严重程度增加无关。这些临床病理学特征表明，TREM2变体通过改变神经元变性和tau依赖性小胶质细胞营养不良的分布，导致海马保留和非遗忘型AD表型，从而导致临床和病理学AD异质性。
Alzheimer’s disease (AD) has multiple clinically and pathologically defined subtypes where the underlying causes of such heterogeneity are not well established. Rare TREM2 variants confer significantly increased risk for clinical AD in addition to other neurodegenerative disease clinical phenotypes. Whether TREM2 variants are associated with atypical clinical or pathologically defined subtypes of AD is not known. We studied here the clinical and pathological features associated with TREM2 risk variants in an autopsy-confirmed cohort. TREM2 variant cases were more frequently associated with non-amnestic clinical syndromes. Pathologically, TREM2 variant cases were associated with an atypical distribution of neurofibrillary tangle density with significantly lower hippocampal NFT burden relative to neocortical NFT accumulation. In addition, NFT density but not amyloid burden was associated with an increase of dystrophic microglia. TREM2 variant cases were not associated with an increased prevalence, extent, or severity of co-pathologies. These clinicopathological features suggest that TREM2 variants contribute to clinical and pathologic AD heterogeneity by altering the distribution of neurofibrillary degeneration and tau-dependent microglial dystrophy, resulting in hippocampal sparing and non-amnestic AD phenotypes.
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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：
Jin, Sheng Chih;Benitez, Bruno A.;Cruchaga, Carlos
通讯作者：
Cruchaga, Carlos
影响因子：
2.9
作者：
Higashi, Shinji;Iseki, Eizo;Arai, Heii
通讯作者：
Arai, Heii
影响因子：
12.7
作者：
Lee EB;Porta S;Michael Baer G;Xu Y;Suh E;Kwong LK;Elman L;Grossman M;Lee VM;Irwin DJ;Van Deerlin VM;Trojanowski JQ
通讯作者：
Trojanowski JQ
DOI：
10.1016/j.jalz.2017.01.014
发表时间：
2017-08
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Crutch SJ;Schott JM;Rabinovici GD;Murray M;Snowden JS;van der Flier WM;Dickerson BC;Vandenberghe R;Ahmed S;Bak TH;Boeve BF;Butler C;Cappa SF;Ceccaldi M;de Souza LC;Dubois B;Felician O;Galasko D;Graff-Radford J;Graff-Radford NR;Hof PR;Krolak-Salmon P;Lehmann M;Magnin E;Mendez MF;Nestor PJ;Onyike CU;Pelak VS;Pijnenburg Y;Primativo S;Rossor MN;Ryan NS;Scheltens P;Shakespeare TJ;Suárez González A;Tang-Wai DF;Yong KXX;Carrillo M;Fox NC;Alzheimer's Association ISTAART Atypical Alzheimer's Disease and Associated Syndromes Professional Interest Area
通讯作者：
Alzheimer's Association ISTAART Atypical Alzheimer's Disease and Associated Syndromes Professional Interest Area