Introduction: We 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. Methods: In 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. Results: All 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. Discussion: Higher 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.
Bibliographical noteFunding Information:
This study was partly funded by ZonMw Memorabel (grant number 73305095005) and Alzheimer Nederland through the Netherlands Consortium of Dementia Cohorts (NCDC) in the context of Deltaplan Dementie. Further funding was obtained from the Netherlands CardioVascular Research Initiative, the Dutch Heart Foundation (CVON 2018‐28 Heart Brain Connection Cross‐roads), Dutch Federation of University Medical Centres, the Netherlands Organisation for Health Research and Development, and the Royal Netherlands Academy of Sciences.
This work was supported by the European Union's Horizon 2020 research and innovation program (grant number 667375; “CoSTREAM”); the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research (NWO; grant numbers 948‐00‐010, 918‐46‐615); the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Ministry of Education, Culture and Science; the Ministry of Health, Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam.
© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association