Description

Cerebrospinal fluid amyloid beta 42, total tau, and phosphorylated tau 181 are well accepted markers of Alzheimer’s disease. These biomarkers better reflect disease pathogenesis compared to clinical diagnosis. Identifying genes/loci that regulate the levels of these biomarkers can help us uncover novel biological pathways involved in the disease mechanism. We performed a GWAS meta-analysis including 18,948 individuals of European ancestry from 30 different cohorts, including the Knight-ADRC, ADNI, DIAN, ALFA+, EADB among others. This is the largest study to date for the three CSF biomarkers.

Principal Investigators

  • Carlos Cruchaga — Washington University in St. Louis

Funding Sources

This work was supported by grants from the National Institutes of Health (R01AG044546 (CC), P01AG003991(CC, JCM), RF1AG053303 (CC), RF1AG058501 (CC), U01AG058922 (CC), RF1AG074007 (YJS)), the Chan Zuckerberg Initiative (CZI), the Michael J. Fox Foundation (CC), the Department of Defense (LI- W81XWH2010849), and the Alzheimer’s Association Zenith Fellows Award (ZEN-22-848604, awarded to CC). Other cohort specific grants included a grant (European Alzheimer DNA BioBank, EADB) from the EU Joint Programme, Neurodegenerative Disease Research (JPND), agency for Innovation and Entrepreneurship (VLAIO) grant No PR067/21 and EU/EFPIA Innovative Medicines Initiative Joint Undertaking EPAD grant agreement 115736.

Publications

  • Timsina J. GWAS meta-analysis of cerebrospinal fluid Alzheimer's biomarkers reveals loci regulating lipids, brain volume and autophagy. Nature communications. 2026 Apr 21. PubMed link