Higher CSF sTREM2 attenuates ApoE4-related risk for cognitive decline and neurodegeneration.
Higher CSF sTREM2 attenuates ApoE4-related risk for cognitive decline and neurodegeneration.
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DOI：
10.1186/s13024-020-00407-2
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发表时间：
2020-10-08
影响因子：
15.1
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative (ADNI)
中科院分区：
文献类型：
--
作者：
Franzmeier N;Suárez-Calvet M;Frontzkowski L;Moore A;Hohman TJ;Morenas-Rodriguez E;Nuscher B;Shaw L;Trojanowski JQ;Dichgans M;Kleinberger G;Haass C;Ewers M;Alzheimer’s Disease Neuroimaging Initiative (ADNI)
载脂蛋白Eε4等位基因(即载脂蛋白E4)是散发性阿尔茨海默病(AD)最强的遗传危险因素。TREM2(即触发髓系细胞上表达的受体2)是一种小胶质细胞跨膜蛋白，在阿尔茨海默病(AD)脑病变的小胶质细胞激活中发挥核心作用。较高的TREM2相关小胶质细胞活性是否调节了发生临床AD的风险仍是一个悬而未决的问题。因此，目前这项研究的目的是评估较高的sTREM2是否能减弱载脂蛋白E4-对未来认知能力下降和神经退化的影响。我们纳入了来自阿尔茨海默病神经成像计划的708名受试者，范围从认知正常(CN，n = 221)到轻度认知障碍(MC I，n = 414)和AD痴呆(n = 73)。我们使用线性回归来检验脑脊液评估的sTREM2水平作为纵向评估的认知功能下降的预测因子和磁共振评估的海马区体积变化(平均随访4 年，范围为1.7-7 年)之间的交互作用。在整个样本中，我们发现基线时较高的脑脊液sTREM2与载脂蛋白E4携带(即sTREM2 x载脂蛋白E4相互作用)对纵向整体认知(p = 0.001，科恩的f2 = 0.137)和记忆下降(p = 0.006，科恩的f2 = 0.104)以及纵向评估的海马区萎缩(p = 0.046，科恩的f2 = 0.089)的减弱效应有关，与脑脊液的原发AD病理标记物(即Aβ1-42，p-tau181)无关。虽然sTREM2的总体影响很小，但按诊断组分层的探索性亚分析显示，sTREM2的有益效果在MCI组显著。我们的结果表明，较高的脑脊液sTREM2水平与ApoE4相关的未来认知下降和AD典型神经变性的风险降低有关。这些发现进一步证明，TREM2可能对AD的发展具有保护作用。
The Apolipoprotein E ε4 allele (i.e. ApoE4) is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). TREM2 (i.e. Triggering receptor expressed on myeloid cells 2) is a microglial transmembrane protein brain that plays a central role in microglia activation in response to AD brain pathologies. Whether higher TREM2-related microglia activity modulates the risk to develop clinical AD is an open question. Thus, the aim of the current study was to assess whether higher sTREM2 attenuates the effects of ApoE4-effects on future cognitive decline and neurodegeneration. We included 708 subjects ranging from cognitively normal (CN, n = 221) to mild cognitive impairment (MCI, n = 414) and AD dementia (n = 73) from the Alzheimer’s disease Neuroimaging Initiative. We used linear regression to test the interaction between ApoE4-carriage by CSF-assessed sTREM2 levels as a predictor of longitudinally assessed cognitive decline and MRI-assessed changes in hippocampal volume changes (mean follow-up of 4 years, range of 1.7-7 years). Across the entire sample, we found that higher CSF sTREM2 at baseline was associated with attenuated effects of ApoE4-carriage (i.e. sTREM2 x ApoE4 interaction) on longitudinal global cognitive (p = 0.001, Cohen’s f2 = 0.137) and memory decline (p = 0.006, Cohen’s f2 = 0.104) as well as longitudinally assessed hippocampal atrophy (p = 0.046, Cohen’s f2 = 0.089), independent of CSF markers of primary AD pathology (i.e. Aβ1–42, p-tau181). While overall effects of sTREM2 were small, exploratory subanalyses stratified by diagnostic groups showed that beneficial effects of sTREM2 were pronounced in the MCI group. Our results suggest that a higher CSF sTREM2 levels are associated with attenuated ApoE4-related risk for future cognitive decline and AD-typical neurodegeneration. These findings provide further evidence that TREM2 may be protective against the development of AD.
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影响因子：
3.2
作者：
Crane, Paul K.;Carle, Adam;Gibbons, Laura E.;Insel, Philip;Mackin, R. Scott;Gross, Alden;Jones, Richard N.;Mukherjee, Shubhabrata;Curtis, S. McKay;Harvey, Danielle;Weiner, Michael;Mungas, Dan
通讯作者：
Mungas, Dan
DOI：
10.1084/jem.20142322
发表时间：
2015-03-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jay TR;Miller CM;Cheng PJ;Graham LC;Bemiller S;Broihier ML;Xu G;Margevicius D;Karlo JC;Sousa GL;Cotleur AC;Butovsky O;Bekris L;Staugaitis SM;Leverenz JB;Pimplikar SW;Landreth GE;Howell GR;Ransohoff RM;Lamb BT
通讯作者：
Lamb BT
影响因子：
14.5
作者：
Hamelin, Lorraine;Lagarde, Julien;Sarazin, Marie
通讯作者：
Sarazin, Marie
TREM2 通过抑制小胶质细胞炎症反应来改善神经元 Tau 病理学。
影响因子：
5.1
作者：
Jiang, Teng;Zhang, Ying-Dong;Zhou, Jun-Shan
通讯作者：
Zhou, Jun-Shan
DOI：
10.1016/j.jalz.2018.01.010
发表时间：
2018-11
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Hansson O;Seibyl J;Stomrud E;Zetterberg H;Trojanowski JQ;Bittner T;Lifke V;Corradini V;Eichenlaub U;Batrla R;Buck K;Zink K;Rabe C;Blennow K;Shaw LM;Swedish BioFINDER study group;Alzheimer's Disease Neuroimaging Initiative
通讯作者：
Alzheimer's Disease Neuroimaging Initiative