AbstractIntroductionWe investigated how components of immunity relate to biomarkers of Alzheimer's disease (AD) in plasma and explored the influence of AD genetic risk factors in the population‐based Rotterdam Study.MethodsIn 7397 persons, we calculated the granulocyte‐to‐lymphocyte ratio (GLR), platelet‐to‐lymphocyte ratio (PLR), and systemic immune‐inflammation index (SII). In 3615 of these persons, plasma amyloid‐beta (Aβ)42 and Aβ40 were measured. Next, we constructed an overall genetic risk score (GRS) based on genome‐wide significant variants, both including and excluding APOE ε4.ResultsAll innate immunity phenotypes were related to higher Aβ, most strongly with a doubling in GLR leading to a 1.9% higher Aβ42 (95% confidence interval [95% CI] 0.4 to 3.3%) and 3.2% higher Aβ40 (95% CI 2.0 to 4.3%). Higher AD GRS including APOE ε4 was associated with higher immunity markers.DiscussionHigher levels of immunity markers were associated with higher Aβ in plasma. Participants with a higher genetic predisposition to AD had higher immunity markers, where these effects were mainly driven by APOE ε4.