Systemic inflammation and causal risk for Alzheimer's dementia: Possibilities and limitations of a Mendelian randomization approach

Epidemiological studies have implicated systemic inflammation in the development of Alzheimer's disease (AD). However, these observations have been subject to residual confounding and reverse causation. We applied Mendelian randomization approaches to address this. We did not identify any causal associations between serum interleukin (IL)-18, IL-1ra, IL-6, or erythrocyte sedimentation rate (ESR) concentrations and AD. Our findings are limited by the low number of available instruments, though some of those identified (e.g., IL-6) were of sufficient power to indicate true negative results. Taken together, it appears there is no evidence for a causal association between these serum inflammatory cytokines and AD