Polygenic risk scores for LATE‐neuropathologic change: Implications for clinical utility
Jung‐Min Pyun, Young Ho Park, Lincoln M. P. Shade, David W. Fardo, SangYun Kim, Kwangsik Nho,Abstract
INTRODUCTION
Limbic‐predominant age‐related TDP‐43 encephalopathy (LATE) exhibits clinical features resembling Alzheimer's disease (AD) and frequently occurs as a co‐pathology, yet there are fewer biomarkers for LATE relative to AD.
METHODS
We calculated polygenic risk scores for LATE‐neuropathologic change (LATE‐PRS) and performed association analysis with neuropathology ( N = 99) and longitudinal cognitive change rates ( N = 538) in Alzheimer's Disease Neuroimaging Initiative participants aged ≥ 75 years, stratified by amyloid positron emission tomography (PET) positivity status.
RESULTS
LATE‐PRS was significantly associated with pathologically confirmed LATE (odds ratio = 2.292, P = 0.002), independent of AD pathology. In cognitively impaired individuals, LATE‐PRS was associated with faster executive function decline in PET‐negative individuals (β = –0.002, P = 0.041), and faster memory (β = –0.002, P < 0.001) and executive function (β = –0.001, P = 0.035 ) decline in PET‐positive individuals. In the overall sample, associations were significant only in the PET‐negative individuals.
DISCUSSION
LATE‐PRS may serve as a potential biomarker for LATE risk and cognitive progression.