Association of the top 20 Alzheimer's disease risk genes with [F]flortaucipir PET.

INTRODUCTION

We previously reported genetic associations of the top Alzheimer's disease (AD) risk alleles with amyloid deposition and neurodegeneration. Here, we report the association of these variants with [F]flortaucipir standardized uptake value ratio (SUVR).

METHODS

We analyzed the [F]flortaucipir scans of 352 cognitively normal (CN), 160 mild cognitive impairment (MCI), and 54 dementia (DEM) participants from Alzheimer's Disease Neuroimaging Initiative (ADNI)2 and 3. We ran step-wise regression with log-transformed [F]flortaucipir meta-region of interest SUVR as the outcome measure and genetic variants, age, sex, and apolipoprotein E () ε4 as predictors. The results were visualized using parametric mapping at familywise error cluster-level-corrected < .05.

RESULTS

ε4 showed significant ( < .05) associations with tau deposition across all disease stages. Other significantly associated genes include variants in in CN, in MCI, and in MCI and dementia participants.

DISCUSSION

We found significant associations to tau deposition for , , , and , in addition to ε4. These four variants have been previously associated with tau metabolism through model systems.