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, p < 0.0001). AAs were more likely to carry TREM2 coding variants (15% vs 3%, p < 0.0001), which were associated with lower CSF sTREM2. AAs were less likely to carry the rs1582763 minor allele (8% vs 37%, p < 0.0001), located near MS4A4A, 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 (p = 0.03), AAs were more likely to carry coding TREM2 variants (22% vs 4%, p = 0.002), and AAs were less likely to carry the rs1582763 minor allele (16% vs 37%, p = 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.

为了评估在髓样细胞 2 (TREM2) 上表达的触发受体的种族差异，TREM2 是阿尔茨海默病的关键免疫介质，CSF 可溶性 TREM2 (sTREM2) 的水平以及相关遗传变异的频率在自测个体组中进行了比较- 将他们的种族报告为非裔美国人 (AA) 或非西班牙裔白人 (NHW)。

社区居住的老年研究参与者接受了脑脊液 sTREM2 浓度测量和遗传分析。

主要队列包括 91 名 AA 和 868 名 NHW。与 NHW 组相比，AA 组的 CSF sTREM2 水平较低（1,336 ± 470 对 1,856 ± 624 pg/mL，p < 0.0001）。AA 更有可能携带TREM2编码变体（15% 对 3%，p < 0.0001），这与较低的 CSF sTREM2 相关。AA 不太可能携带位于MS4A4A附近的 rs1582763 次要等位基因（8% 对 37%， p < 0.0001） ，这与较高的 CSF sTREM2 相关。这些发现在 23 个 AA 和 917 个 NHW 的独立队列中得到重复：AA 组的 CSF sTREM2 水平较低 ( p = 0.03)，AA 更有可能携带编码TREM2变体（22% 对 4%，p= 0.002)，并且 AA 不太可能携带 rs1582763 次要等位基因（16% 对 37%，p = 0.003）。

平均而言，与 NHW 相比，AA 的 CSF sTREM2 水平较低，这可能是因为 AA 更有可能携带与较低 CSF sTREM2 水平相关的遗传变异。重要的是，CSF 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遗传变异风险有关。