Genome-wide association study of brain tau deposition as measured by F-flortaucipir positron emission tomography imaging.

Neurobiol Aging

Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.

Published: December 2022

AI Article Synopsis

  • The study investigates genetic variants linked to tau deposition, a key feature of Alzheimer's disease, through a genome-wide association study in 543 non-demented Europeans.
  • Two novel genetic variants, rs56298435 in the ZBTB20 gene and rs150532 in the EYA4 gene, were associated with higher levels of tau as measured by PET imaging.
  • The findings suggest that these genetic factors potentially influence cognitive decline via the effects on tau pathology, indicating a hereditary component to tau deposition in the brain.

Article Abstract

The related genetic variants of tau deposition, a seminal pathological hallmark of Alzheimer's disease, remain poorly understood. We sought to perform a genome-wide association study of brain tau load as measured by AV1451 positron emission tomography (PET). Among 543 non-demented European individuals, novel associations with higher tau were identified for rs56298435 (p = 8.35 × 10, β=0.31) within ZBTB20, and for rs150532 (p = 1.90 × 10, β=0.26) in the protein phosphorylation regulatory gene EYA4. The APOE association additionally reached genome-wide significant when APOE ε4 was not adjusted. Minor allele carriers of rs56298435 or rs150532 showed higher levels of tau PET load. As expected, phosphorylated-tau analyses in both plasma and cerebrospinal fluid also revealed the same direction of effect. Functionally, the effects of novel loci on cognitive decline could be mediated by tau pathology. In addition, we observed that the expression of VNN2 as regulated by rs150532, together with EYA4, displayed significant correlations with the tau-related gene MAPT in numerous brain regions. Our novel finding lends additional credence to heritable underpinnings of tau deposition.

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http://dx.doi.org/10.1016/j.neurobiolaging.2022.09.002DOI Listing

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