Schindler Suzanne E, Cruchaga Carlos, Joseph Amulya, McCue Lena, Farias Fabiana H G, Wilkins Consuelo H, Deming Yuetiva, Henson Rachel L, Mikesell Robert J, Piccio Laura, Llibre-Guerra Jorge J, Moulder Krista L, Fagan Anne M, Ances Beau M, Benzinger Tammie L S, Xiong Chengjie, Holtzman David M, Morris John C
Department of Neurology (S.E.S., A.J., R.L.H., R.J.M., L.P., J.J.L.-G., K.L.M., A.M.F., D.M.H., J.C.M.), Department of Psychiatry (C.C., F.H.G.F.), and Division of Biostatistics (L.M., C.X.), Washington University School of Medicine, St. Louis, MO; Office of Health Equity and Department of Medicine (C.H.W.), Division of Geriatrics, Vanderbilt University Medical Center, Nashville, TN; Department of Internal Medicine (C.H.W.), Meharry Medical College, Nashville, TN; Alzheimers Disease Research Center (Y.D.), University of Wisconsin School of Medicine and Public Health, Madison; Brain and Mind Centre (L.P.), University of Sydney, NSW, Australia; and Mallinckrodt Institute of Radiology (B.M.A., T.L.S.B.), Washington University School of Medicine, St. Louis, MO.
Neurol Genet. 2021 Mar 4;7(2):e571. doi: 10.1212/NXG.0000000000000571. eCollection 2021 Apr.
To evaluate for racial differences in triggering receptor expressed on myeloid cells 2 (TREM2), a key immune mediator in Alzheimer disease, the levels of CSF soluble TREM2 (sTREM2), and the frequency of associated genetic variants were compared in groups of individuals who self-reported their race as African American (AA) or non-Hispanic White (NHW).
Community-dwelling older research participants underwent measurement of CSF sTREM2 concentrations and genetic analyses.
The primary cohort included 91 AAs and 868 NHWs. CSF sTREM2 levels were lower in the AA compared with the NHW group (1,336 ± 470 vs 1,856 ± 624 pg/mL, < 0.0001). AAs were more likely to carry coding variants (15% vs 3%, < 0.0001), which were associated with lower CSF sTREM2. AAs were less likely to carry the rs1582763 minor allele (8% vs 37%, < 0.0001), located near , which was associated with higher CSF sTREM2. These findings were replicated in an independent cohort of 23 AAs and 917 NHWs: CSF sTREM2 levels were lower in the AA group ( = 0.03), AAs were more likely to carry coding variants (22% vs 4%, = 0.002), and AAs were less likely to carry the rs1582763 minor allele (16% vs 37%, = 0.003).
On average, AAs had lower CSF sTREM2 levels compared with NHWs, potentially because AAs are more likely to carry genetic variants associated with lower CSF sTREM2 levels. Importantly, CSF sTREM2 reflects TREM2-mediated microglial activity, a critical step in the immune response to amyloid plaques. These findings suggest that race may be associated with risk for genetic variants that influence Alzheimer disease-related inflammation.
评估髓系细胞触发受体2（TREM2）这一阿尔茨海默病关键免疫介质在种族间的差异，比较自我报告种族为非裔美国人（AA）或非西班牙裔白人（NHW）的个体组中脑脊液可溶性TREM2（sTREM2）水平及相关基因变异的频率。
对社区居住的老年研究参与者进行脑脊液sTREM2浓度测量和基因分析。
主要队列包括91名非裔美国人及868名非西班牙裔白人。与非西班牙裔白人组相比，非裔美国人组的脑脊液sTREM2水平更低（1336±470 vs 1856±624 pg/mL，P<0.0001）。非裔美国人更有可能携带编码变异（15% vs 3%，P<0.0001），这些变异与脑脊液sTREM2水平较低相关。非裔美国人携带rs1582763次要等位基因的可能性较小（8% vs 37%，P<0.0001），该等位基因位于附近，与脑脊液sTREM2水平较高相关。这些发现在一个由23名非裔美国人及917名非西班牙裔白人组成的独立队列中得到重复：非裔美国人组的脑脊液sTREM2水平较低（P=0.03），非裔美国人更有可能携带编码变异（22% vs 4%，P=0.002），且非裔美国人携带rs1582763次要等位基因的可能性较小（16% vs 37%，P=0.003）。
平均而言，与非西班牙裔白人相比，非裔美国人的脑脊液sTREM2水平较低，这可能是因为非裔美国人更有可能携带与脑脊液sTREM2水平较低相关的基因变异。重要的是，脑脊液sTREM2反映了TREM2介导的小胶质细胞活性，这是对淀粉样斑块免疫反应的关键步骤。这些发现表明，种族可能与影响阿尔茨海默病相关炎症的基因变异风险有关。
