A genome-wide association study of longitudinal change in CSF tau among non-demented elders

Tau is a microtubule-binding protein that is critical to the organization and stabilization of microtubules physiologically. Cerebrospinal fluid (CSF) total tau (t-tau) and CSF phosphorylated tau (p-tau) have been recommended as diagnostic biomarkers for AD according to the 2018 National Institute on Aging and Alzheimer’s Association (NIA-AA) research framework. We performed a genome-wide association study (GWAS) of longitudinal change in CSF t-tau among 317 non-demented elders from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort in non-Hispanic Caucasians. We employed the linear regression model to identify novel variants associated with longitudinal change of t-tau in CSF. One single nucleotide polymorphism (SNP) (rs17149074) in the region of C9orf171 (CFAP77) gene was found to reach genome-wide significance associated with longitudinal change of CSF t-tau. Five SNPs (rs10916844, rs10916846, rs9425869, rs3744474, rs8078303) were identified as potential candidate loci associated with longitudinal change of CSF t-tau. Validation of the identified loci in larger samples and various races was needed in future research.