Causal effects of circulating cytokine concentrations on risk of Alzheimer's disease and cognitive function

Pagoni, Panagiota ORCID: https://orcid.org/0000-0002-8090-512X, Korologou-Linden, Roxanna S., Howe, Laura D., Smith, George Davey, Ben-Shlomo, Yoav, Stergiakouli, Evie and Anderson, Emma L. 2022. Causal effects of circulating cytokine concentrations on risk of Alzheimer's disease and cognitive function. Brain, Behavior, and Immunity 104 , pp. 54-64. 10.1016/j.bbi.2022.05.006

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Abstract

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 genome-wide 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 MIP-1b (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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Publisher:	Elsevier
ISSN:	0889-1591
Date of Acceptance:	12 May 2022
Last Modified:	09 Aug 2024 10:30
URI:	https://orca.cardiff.ac.uk/id/eprint/170925

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