GWAS meta-analysis of CSF Alzheimer’s biomarkers reveals novel loci regulating lipids, brain volume and autophagy

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.

PI

Carlos Cruchaga
Washington University in St. Louis

Associated Datasets

NG00191 - GWAS for CSF AD Aβ and tau in 18,948 individuals of European ancestry

We performed a GWAS meta-analysis including 18,948 individuals of European ancestry. This is the largest study to date for the three biomarkers encompassing 30 different studies. Biomarker levels from 6,785…

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Grants

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.

Acknowledgement

Acknowledgment statement for any data distributed by NIAGADS:

Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer's Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689), funded by the National Institute on Aging.

For investigators using GWAS meta-analysis of CSF Alzheimer’s biomarkers reveals novel loci regulating lipids, brain volume and autophagy data:

This work was supported by grants from the National Institutes of Health (R01-AG064614 (CC), U01-AG084514 (CC), P01-NS131131 (CC), R01-AG078964(CC), R01-AG058501 (CC), R01-AG071706 (CC), P30-AG066444 (CC), R01-AG064877 (CC), and the Cure Alzheimer's Fund.

The recruitment and clinical characterization of research participants at Washington University were supported by NIH P30AG066444 (DMH), P01AG03991 (JCM), and P01AG026276 (JCM).

This work was supported by access to equipment made possible by the Hope Center for Neurological Disorders, the NeuroGenomics and Informatics Center (NGI: https://neurogenomics.wustl.edu/) and the Departments of Neurology and Psychiatry at Washington University School of Medicine.

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