Higher CSF sTREM2 and microglia activation are associated with slower rates of beta-amyloid accumulation.
Higher CSF sTREM2 and microglia activation are associated with slower rates of beta-amyloid accumulation.
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DOI：
10.15252/emmm.202012308
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发表时间：
2020-09-07
影响因子：
11.1
通讯作者：
Franzmeier N
中科院分区：
文献类型：
--
作者：
Ewers M;Biechele G;Suárez-Calvet M;Sacher C;Blume T;Morenas-Rodriguez E;Deming Y;Piccio L;Cruchaga C;Kleinberger G;Shaw L;Trojanowski JQ;Herms J;Dichgans M;Alzheimer's Disease Neuroimaging Initiative (ADNI);Brendel M;Haass C;Franzmeier N
小胶质细胞激活是大脑对阿尔茨海默病（AD）淀粉样斑块的主要免疫反应。AD患者脑脊液（CSF）可溶性TREM2 （sTREM2，小胶质细胞活化的生物标志物）和小胶质细胞PET水平均升高；然而，这些生物标志物的增加是否与淀粉样蛋白- β (Aβ)积累减少有关仍不清楚。为了解决这个问题，我们采用了双管齐下的翻译方法。首先，在非痴呆和痴呆个体中，我们在基线时测试了CSF stre2，以预测(i)淀粉样蛋白PET在约2年内的变化，（ii）在一部分患者中横断面评估tau PET。我们发现脑脊液sTREM2升高与淀粉样蛋白PET降低和tau PET降低相关。其次，在App NL‐G-F小鼠淀粉样变性模型中，我们研究了基线18F‐GE180小胶质细胞PET和纵向淀粉样蛋白PET，以测试小胶质细胞与Aβ的关联，没有AD患者中常见的任何混淆共病理。5个月大时较高的小胶质细胞PET与5 - 10个月大时淀粉样蛋白PET增加较慢相关。综上所述，脑脊液sTREM2或小胶质细胞PET测定的高小胶质细胞活化对随后的淀粉样蛋白积累具有保护作用。TREM2是一种在大脑中几乎完全由小胶质细胞表达的蛋白。本研究探讨了人、小鼠脑脊液中可溶性TREM2 （sTREM2）水平与Aβ纵向积累的关系。
Microglia activation is the brain's major immune response to amyloid plaques in Alzheimer's disease (AD). Both cerebrospinal fluid (CSF) levels of soluble TREM2 (sTREM2), a biomarker of microglia activation, and microglia PET are increased in AD; however, whether an increase in these biomarkers is associated with reduced amyloid‐beta (Aβ) accumulation remains unclear. To address this question, we pursued a two‐pronged translational approach. Firstly, in non‐demented and demented individuals, we tested CSF sTREM2 at baseline to predict (i) amyloid PET changes over ∼2 years and (ii) tau PET cross‐sectionally assessed in a subset of patients. We found higher CSF sTREM2 associated with attenuated amyloid PET increase and lower tau PET. Secondly, in the App NL‐G-F mouse model of amyloidosis, we studied baseline 18F‐GE180 microglia PET and longitudinal amyloid PET to test the microglia vs. Aβ association, without any confounding co‐pathologies often present in AD patients. Higher microglia PET at age 5 months was associated with a slower amyloid PET increase between ages 5‐to‐10 months. In conclusion, higher microglia activation as determined by CSF sTREM2 or microglia PET shows protective effects on subsequent amyloid accumulation. TREM2 is a protein almost exclusively expressed by microglia in the brain. This study investigates the association between soluble TREM2 (sTREM2) levels in cerebrospinal fluid and the longitudinal Aβ accumulation in human and mouse.
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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：
14.5
作者：
Hamelin, Lorraine;Lagarde, Julien;Sarazin, Marie
通讯作者：
Sarazin, Marie
影响因子：
15.1
作者：
Bemiller SM;McCray TJ;Allan K;Formica SV;Xu G;Wilson G;Kokiko-Cochran ON;Crish SD;Lasagna-Reeves CA;Ransohoff RM;Landreth GE;Lamb BT
通讯作者：
Lamb BT
影响因子：
11
作者：
Brendel, M.;Jaworska, A.;Rominger, A.
通讯作者：
Rominger, A.
影响因子：
9.3
作者：
Blume T;Focke C;Peters F;Deussing M;Albert NL;Lindner S;Gildehaus FJ;von Ungern-Sternberg B;Ozmen L;Baumann K;Bartenstein P;Rominger A;Herms J;Brendel M
通讯作者：
Brendel M