TREM2 expression in the human brain: a marker of monocyte recruitment?
TREM2 expression in the human brain: a marker of monocyte recruitment?
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DOI：
10.1111/bpa.12564
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发表时间：
2018-09
期刊：
影响因子：
--
通讯作者：
MRC-CFAS
中科院分区：
文献类型：
--
作者：
Fahrenhold M;Rakic S;Classey J;Brayne C;Ince PG;Nicoll JAR;Boche D;MRC-CFAS
骨髓细胞上表达的触发受体 (TREM) 2 基因的突变已被确定为包括阿尔茨海默病 (AD) 在内的多种神经退行性疾病的危险因素。使用 AD 动物模型的实验研究强调了与 TREM2 及其由小胶质细胞表达相关的许多功能。因此，人们推测人类也是如此。然而，有关人脑中 TREM2 细胞表达的信息非常有限。作为使用医学研究委员会认知功能和衰老研究 (MRC-CFAS) 提供的死后资源对小胶质细胞进行研究的一部分，我们使用 Sigma 抗体 HPA010917 对 299 名参与者的大脑皮层进行 TREM2 免疫染色，并与巨噬细胞/小胶质细胞标记物 Iba1 和 CD68 进行比较。正如预期的那样，Iba1 和 CD68 标记了小胶质细胞和血管周围巨噬细胞。然而，在大多数情况下 (284/299)，TREM2 抗体标记血管腔内的单核细胞，但不标记小胶质细胞或血管周围巨噬细胞。相比之下，在 6 例急性梗塞病例中，有 5 例的 TREM2 免疫反应将脑实质内的细胞识别为招募的单核细胞。 6 例陈旧性梗死病例含有吞噬泡沫状巨噬细胞，其 CD68 阳性但 TREM2 阴性。我们使用 HPA010917 抗 TREM2 抗体进行的观察表明，TREM2 并非由小胶质细胞表达，而是似乎是人脑中募集的单核细胞的标记。这一发现对于 TREM2 作为危险因素的作用具有重要意义，强调了全身免疫反应在阿尔茨海默病发生和进展中的重要性。
Mutation in the triggering receptor expressed on myeloid cells (TREM) 2 gene has been identified as a risk factor for several neurodegenerative diseases including Alzheimer's disease (AD). Experimental studies using animal models of AD have highlighted a number of functions associated with TREM2 and its expression by microglial cells. It has therefore been assumed that this is also the case in humans. However, there is very limited information concerning the cellular expression of TREM2 in the human brain. As part of investigations of microglia using post‐mortem resources provided by the Medical Research Council Cognitive Function and Ageing Studies (MRC‐CFAS), we immunostained the cerebral cortex of 299 participants for TREM2 using the Sigma antibody HPA010917 and compared with the macrophage/microglial markers Iba1 and CD68. As expected, Iba1 and CD68 labeled microglia and perivascular macrophages. However, in most cases (284/299), the TREM2 antibody labelled monocytes within vascular lumens, but not microglia or perivascular macrophages. In contrast, in 5 out of 6 cases with acute infarcts, TREM2 immunoreaction identified cells within the brain parenchyma interpreted as recruited monocytes. Six cases with old infarcts contained phagocytic foamy macrophages which were CD68‐positive but TREM2 negative. Our observations, using the HPA010917 anti‐TREM2 antibody, suggest that TREM2 is not expressed by microglia but instead seems to be a marker of recruited monocytes in the human brain. This finding has implications with regards to the role of TREM2 as a risk factor, emphasizing the importance of systemic immune responses in the development and progression of Alzheimer's disease.
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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：
6.1
作者：
Edison, Paul;Archer, Hilary A.;Brooks, David J.
通讯作者：
Brooks, David J.
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：
3.4
作者：
Fumagalli S;Perego C;Pischiutta F;Zanier ER;De Simoni MG
通讯作者：
De Simoni MG
影响因子：
5.3
作者：
Kitazawa, M;Oddo, S;LaFerla, FM
通讯作者：
LaFerla, FM