Large-scale GWAS meta-analysis of CSF AD biomarkers

25. April 2026

Cerebrospinal fluid (CSF) levels of amyloid beta 42 (Aβ42), total tau, and phosphorylated tau 181 (p-tau181) are among the most established biomarkers for Alzheimer’s disease (AD), offering a closer window onto disease pathogenesis than clinical diagnosis alone. In a new collaborative effort, a large international consortium — including LIGA head Dr. Lars Bertram as co-senior author — has now published the hitherto largest GWAS meta-analysis of these three CSF biomarkers in Nature Communications. The study, led by colleagues from Washington University in St. Louis, pooled data from 18,948 individuals of European ancestry across multiple cohorts, including the EMIF-AD dataset contributed by our group. Across the three biomarkers, the analysis identified 12 genome-wide significant loci, eight of which are novel. Functional follow-up analyses implicate these genes in lipid metabolism (independent of APOE), autophagy, and brain volume regulation — biological pathways not readily captured by conventional case-control GWAS designs. The findings underscore the value of quantitative endophenotypes such as CSF biomarkers for uncovering disease mechanisms and identifying novel therapeutic targets for AD. The full text of this study can be found on the Nature Communications website (https://doi.org/10.1038/s41467-026-71682-8).