Skip to content
DraconiticResearch
Search Sources API
182,469 studies31 sourcesUpdated 24 min ago
Peer-reviewedCC BY-NC-NDAlzheimer's & dementia : the journal of the Alzheimer's Association

Polygenic risk scores for LATE-neuropathologic change: Implications for clinical utility.

  • Jung-Min Pyun1
  • Young Ho Park1
  • Lincoln M P Shade2
  • David W Fardo2
  • SangYun Kim1
  • Kwangsik Nho3,4
  • Alzheimer's Disease Neuroimaging Initiative
4 affiliations
  1. 1Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam, Republic of Korea.
  2. 2Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky, USA.
  3. 3Department of Radiology and Imaging Sciences, and the Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.
  4. 4Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Read full textPDFDOICite

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.

Related

  1. Hybrid risk scores integrating polygenic and clinical variables for endometriosis prediction
    O. Goroshchuk, D. Koller
    medRxivPreprintAll rights reservedFull textEpidemiology & public healthmedRxiv
  2. Agile scores in MASLD and ALD: External validation and their utility in clinical algorithms
    Margarita Papatheodoridi, Victor de Ledinghen, Monica Lupsor-Platon +18
    Journal of HepatologyPeer-reviewedLicence not statedFull text34 citedEpidemiology & public healthHAL
  3. A clinical laboratory test-wide association scan of polygenic scores identifies biomarkers of psychiatric disorders
    M. L. Reed, K. L. Feuer, R. L. Kember
    medRxivPreprintCC BY-NC-NDFull textHuman geneticsmedRxiv
  4. Implementing polygenic risk scores for breast cancer prevention: protocol for a feasibility study in a real-world clinical setting
    Sara Farina, Francesco Andrea Causio, Pietro Eric Risuleo +13
    BMJ OpenPeer-reviewedCC BY-NC 4.0Full textEpidemiology & public healthCrossrefDOAJPMC
  5. Pathway-Specific Polygenic Scores for Predicting Clinical Lithium Treatment Response in Patients With Bipolar Disorder
    Nigussie Sharew, Scott Clark, Sergi Papiol +159
    Biological Psychiatry Global Open SciencePeer-reviewedCC BY-NC-ND9 citedPsychiatry & mental healthHAL

Cite

BibTeXRIS
BibTeX
@article{pyun2026polygenic,
  title = {{Polygenic risk scores for LATE-neuropathologic change: Implications for clinical utility.}},
  author = {Jung-Min Pyun and Young Ho Park and Lincoln M P Shade and David W Fardo and SangYun Kim and Kwangsik Nho and Alzheimer's Disease Neuroimaging Initiative},
  journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
  year = {2026},
  month = oct,
  doi = {10.1002/alz.71824},
  url = {https://europepmc.org/article/MED/42963336},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Polygenic risk scores for LATE-neuropathologic change: Implications for clinical utility.
AU  - Jung-Min Pyun
AU  - Young Ho Park
AU  - Lincoln M P Shade
AU  - David W Fardo
AU  - SangYun Kim
AU  - Kwangsik Nho
AU  - Alzheimer's Disease Neuroimaging Initiative
PY  - 2026
DA  - 2026/10/01
JO  - Alzheimer's & dementia : the journal of the Alzheimer's Association
DO  - 10.1002/alz.71824
UR  - https://europepmc.org/article/MED/42963336
AB  - 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.
SN  - 1552-5260
SN  - 1552-5279
ER  -