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Updated: Nov 8, 2025
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
African Americans Have Differences in CSF Soluble TREM2 and Associated Genetic Variants
Suzanne E Schindler1, Carlos Cruchaga1, Amulya Joseph1
1Department 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.
Objective:
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).
Methods:
Community-dwelling older research participants underwent measurement of CSF sTREM2 concentrations and genetic analyses.
Results:
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).
Conclusions:
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.
