African Americans More Likely to Carry Genetic Variants Associated With Dementia

African Americans are more likely than nonhispanic White Americans to carry genetic variants associated with lower cerebrospinal fluid (CSF) soluble triggering receptor expressed on myeloid cells 2 (sTREM2), an immune mediator in Alzheimer disease (AD), according to study results published in Neurology Genetics.

The study was an examination of CSF sTREM2 levels and genetic analyses in community-dwelling older adults with and without cognitive impairment. Those included in this study had previously participated in research focused on memory and aging. Study researchers classified participants as African American (n=91) or nonhispanic White (n=868).

Overall, African American participants were significantly younger than those in the nonhispanic White group (66.1±8.2 vs 69.3±9.2 years, respectively; P =.002). Additionally, African Americans were less likely to have dementia (13% vs 25%, respectively; P =.01), less likely to report a family history of dementia (44% vs 56%, respectively; P =.03), and reported fewer years of education (15.2±2.9 vs 15.9±2.7, respectively; P =.02).

The levels of CSF sTREM2 were significantly lower in African Americans compared with participants who identified as nonhispanic White (1336±470 vs 1856±624 pg/mL, respectively; P <.0001). African Americans were also more likely to carry TREM2 coding variants associated with lower CSF sTREM2 (15% vs 3%, respectively; P <.0001). In addition, African Americans were significantly less likely to carry the rs1582763 minor allele located near MS4A4A, which is associated with higher CSF sTREM2 (8% vs 37%, respectively; P <.0001).

In an independent cohort consisting of 23 African Americans and 917 nonhispanic White participants, levels of CSF sTREM2 were also lower in participants who identified as African American (P =.03). Similarly, African Americans were also more likely to carry coding TREM2 variants (22% vs 4%, respectively; P =.002) and less likely to carry the rs1582763 minor allele (16% vs 37%, respectively; P =.003) compared with nonhispanic white participants.

A major limitation of this study was the small number of participants in the African American group relative to the nonhispanic White group.

The study investigators concluded that the “development of AD therapies that are less likely to be effective in AA would further compound longstanding injustices experienced by AA” and that their “study underscores the importance of carefully evaluating the effects of race on AD pathophysiology.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Schindler SE, Cruchaga C, Joseph A, et al. African Americans gave differences in CSF soluble TREM2 and associated genetic variants. Published online March 4, 2021. Neurol Genet. doi:10.1212/NXG.0000000000000571