期刊
BRAIN BEHAVIOR AND IMMUNITY
卷 104, 期 -, 页码 54-64出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2022.05.006
关键词
Neuroinflammation; Cytokines; Alzheimer?s disease; Cognitive function; Mendelian randomization
资金
- BRACE Alzheimer?s Disease charity [BR16/028]
- University of Bristol [MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6]
- UK Medical Research Council [215193/Z18/Z]
- Wellcome Trust [MR/P014437/1]
- MRC Skills Development Award from the UK Medical Research Council [MR/M020894/1]
- Career Development Award from the UK Medical Research Council
This study suggests a causal role of cytokines in the pathogenesis of Alzheimer's disease and fluid intelligence.
Background: There is considerable evidence suggesting a role of neuroinflammation in the pathogenesis of Alzheimer's disease. Establishing causality is challenging due to bias from reverse causation and residual confounding.Methods: We used two-sample MR to explore causal effects of circulating cytokine concentrations on Alzheimer's disease risk and cognitive function. We employed genetic variants from the largest publicly available genomewide association studies (GWASs) of cytokine concentrations (N = 8,293), Alzheimer's disease (71,880 cases/ 383,378 controls), prospective memory (N = 152,605 to 462,302), reaction time (N = 454,157 to 459,523) and fluid intelligence (N = 149,051).Results: Evidence suggest that 1 standard deviation (SD) increase in levels of CTACK (CCL27) (OR = 1.09 95%CI: 1.01 to 1.19, p = 0.03) increased risk of Alzheimer's disease. There was weak evidence of a causal effect of MIP1b (CCL4) (OR = 1.04 95% CI: 0.99 to 1.09, p = 0.08), Eotaxin (OR = 1.08 95% CI: 0.99 to 1.17, p = 0.10), GROa (CXCL1) (OR = 1.04 95% CI: 0.99 to 1.10, p = 0.15), MIG (CXCL9) (OR = 1.17 95% CI: 0.97 to 1.41, p = 0.10), IL-8 (Wald ratio: OR = 1.21 95% CI: 0.97 to 1.51, p = 0.09) and IL-2 (Wald Ratio: OR = 1.21 95% CI: 0.94 to 1.56, p = 0.14) on Alzheimer's disease risk. A 1 SD increase in concentration of Eotaxin (IVW: OR = 1.05 95% CI: 0.98 to 1.13, p = 0.14), IL-8 (OR = 1.21 95% CI: 1.07 to 1.37, p = 0.003) and MCP1 (OR = 1.07 95% CI: 1.03 to 1.13, p = 0.003) were associated with lower fluid intelligence, and IL-4 (OR = 0.86 95%CI: 0.79 to 0.98, p = 0.02) with higher.Conclusions: Our findings suggest a causal role of cytokines in the pathogenesis of Alzheimer's disease and fluid intelligence.
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