Exploratory Analysis of APOE ε4-Stratified Associations Between Plasma Alzheimer's Biomarkers and Retinal Imaging Metrics in Cognitively Normal Adults.

@article{choi2026exploratory,
  title = {{Exploratory Analysis of APOE ε4-Stratified Associations Between Plasma Alzheimer's Biomarkers and Retinal Imaging Metrics in Cognitively Normal Adults.}},
  author = {Alex Choi and Alice Haystead and Rachel D'Cunha and John Hsu and Michael Zhu and Kim G Johnson and Michael W Lutz and Heather Whitson and Dilraj S Grewal and Sharon Fekrat},
  journal = {Translational vision science \& technology},
  year = {2026},
  month = oct,
  doi = {10.1167/tvst.15.10.6},
  url = {https://europepmc.org/article/MED/42836717},
  note = {CC BY-NC-ND},
}

TY  - JOUR
TI  - Exploratory Analysis of APOE ε4-Stratified Associations Between Plasma Alzheimer's Biomarkers and Retinal Imaging Metrics in Cognitively Normal Adults.
AU  - Alex Choi
AU  - Alice Haystead
AU  - Rachel D'Cunha
AU  - John Hsu
AU  - Michael Zhu
AU  - Kim G Johnson
AU  - Michael W Lutz
AU  - Heather Whitson
AU  - Dilraj S Grewal
AU  - Sharon Fekrat
PY  - 2026
DA  - 2026/10/01
JO  - Translational vision science & technology
DO  - 10.1167/tvst.15.10.6
UR  - https://europepmc.org/article/MED/42836717
AB  - Purpose  Retinal imaging offers a noninvasive window into microvascular and neurodegenerative changes, yet its relationship to circulating plasma biomarkers of Alzheimer's disease (AD) remains incompletely understood. We evaluated associations between plasma AD biomarkers and retinal imaging metrics in cognitively normal adults and whether these differ by apolipoprotein E (APOE) ε4 status.Methods  This cross-sectional analysis included cognitively normal participants prospectively enrolled from the Duke/UNC Alzheimer's Disease Research Center. Eighty-three eyes from 44 participants (20 APOE ε4 carriers, 24 noncarriers) underwent optical coherence tomography (OCT) and OCT angiography (OCTA) within 1 year of plasma sampling. Plasma AD biomarkers were assessed for associations with structural OCT and microvascular OCTA metrics. Linear mixed-effects models adjusted for age, sex, treated hypertension, and years of education were used, with interaction terms for APOE ε4 status followed by stratified analyses.Results  Nominally significant APOE ε4-dependent interactions were observed between Aβ42/40 and neurofilament light chain (NfL) with ganglion cell-inner plexiform layer (GCIPL) thickness (uncorrected P = 0.026 and P = 0.028). For OCTA, multiple nominally significant APOE ε4-dependent interactions were identified between plasma biomarkers (NfL, pTau217/Aβ42, and pTau217) and perfusion and vessel density across macular regions (uncorrected P = 0.009-0.048). Stratified analyses suggested stronger or more positive relationships in noncarriers, with attenuated or inverse relationships in carriers. None of the associations remained significant after false discovery rate (FDR) correction.Conclusions  In this exploratory analysis, the APOE ε4 genotype may modify associations between plasma AD biomarkers and retinal structural and microvascular metrics in cognitively normal adults.Translational relevance  These exploratory findings support further investigation of whether APOE ε4 genotype-status should be considered in future studies integrating retinal imaging and plasma biomarkers in preclinical Alzheimer's disease.
SN  - 2164-2591
ER  -