Polygenic Hazard Score and Amyloid PET Imaging Mediation Analysis in Alzheimer's Disease Diagnosis

This work studies the mediating role of amyloid PET imaging quantitative traits (QTs) in the relationship between genetic risk, measured by the Polygenic Hazard Score (PHS), and Alzheimer's disease (AD) diagnosis. Data are obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including 559 participants classified as Normal (NL), early mild cognitive impairment (EMCI), late mild cognitive impairment (LMCI), or AD. Thirteen amyloid QTs from AV45 PET scans are examined as potential mediators between PHS and diagnostic outcomes using mediation analysis, Chow tests, and mixed-effects models. Results indicate partial mediation for all QTs in multiple diagnostic comparisons, with both direct and indirect effects being statistically significant. These findings suggest that amyloid PET measures explain part, but not all, of the link between genetic predisposition and AD diagnosis.

The publisher's final version of this work can be found at https://doi.org/10.30574/ijsra.2023.10.2.0980.

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