Work

Assessing the repurposing potential of disease-modifying antirheumatic drug targets to reduce Alzheimer's disease risk: a Mendelian randomization study

Year: 2026

Type: article

Abstract: Systemic inflammation plays a key role in the development and progression of Alzheimer’s disease (AD). However, the repurposing potential of select anti-inflammatory drug targets for AD treatment remains unclear. Two-sample Mendelian randomization (MR) and colocalization analyses were conducted to estimate the effects of select disease-modifying antirheumatic (DMARD) targets on AD risk. We investigated 9 DMARD targets, using blood protein quantitative trait loci (pQTLs) from the UK Biobank Pharma Proteomics Project ( n = 54,219). Outcome associations were extracted from the International Genomics of Alzheimer’s Project ( n cases = 21,982, n controls = 41,944). Our MR estimates suggest that higher levels of FCGR3B , an etanercept target, increased the risk of AD (OR: 1.10; 95% CI [1.02, 1.19]; p = 0.01). We found little evidence that the remaining DMARD targets affected AD risk. Colocalization analysis provided little evidence that target pQTLs, including FCGR3B , colocalized with AD. Our findings suggest a causal effect of FCGR3B on AD risk, but not for the remainder of the analyzed DMARD targets. Further research is recommended to elucidate the causal role of FCGR3B in AD and build upon the current literature on viable AD therapeutic targets. • This is the first Mendelian randomization and colocalization study on select DMARD targets and AD risk. • Mendelian randomization suggests that higher plasma FCGR3B levels increased the risk of AD. • There was little evidence of an effect for the remaining targets. • This suggests that the majority of these targets in plasma are unlikely to be effective candidates for reducing risk of AD.

Source: Brain Behavior & Immunity - Health

DOI: 10.1016/j.bbih.2026.101185

Authors: Christina N. Kushnir, Victoria Taylor-Bateman, Neil M. Davies, Emma L. Anderson

Institutions: University College London, Norwegian University of Science and Technology

Language: English

Topic: Alzheimer's disease research and treatments

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,890