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Biomarkers.

Alex Choi1, Hemal Patel2, Sandra Stinnett3

  • 1Duke University School of Medicine, Durham, NC, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
PubMed
Summary
This summary is machine-generated.

APOE ε4 carriers show retinal microvasculature differences compared to noncarriers, potentially indicating early Alzheimer's disease (AD) biomarkers. Alzheimer's disease patients had distinct retinal changes, suggesting differing disease progression.

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Area of Science:

  • Ophthalmology
  • Neurology
  • Genetics

Background:

  • Alzheimer's disease (AD) is a neurodegenerative disorder.
  • The APOE ε4 allele is a significant genetic risk factor for late-onset AD.
  • Retinal changes may serve as early biomarkers for neurodegenerative diseases like AD.

Purpose of the Study:

  • To investigate differences in retinal structure and microvasculature.
  • Compare individuals with Alzheimer's disease (AD), APOE ε4 carriers, and APOE ε4 noncarriers.
  • Identify potential early AD biomarkers in the retina.

Main Methods:

  • Optical coherence tomography (OCT) angiography was used to analyze retinal vessel density (VD) and perfusion density (PD).
  • Measurements included peripapillary capillary perfusion density (CPD) and retinal thickness parameters (RNFL, GC-IPL, CST).
  • Participants with diabetes, glaucoma, or vitreoretinal pathology were excluded; age and sex-adjusted generalized estimating equations were applied.

Main Results:

  • APOE ε4 carriers showed significantly lower 6mm circle PD and 6mm inner ring VD compared to noncarriers.
  • Individuals with AD had significantly lower CST, 6mm circle PD, 6mm circle VD, and 6mm inner ring VD compared to ε4 noncarriers.
  • AD patients exhibited significantly higher peripapillary CPD compared to both ε4 carriers and noncarriers.

Conclusions:

  • APOE ε4 carriers may exhibit early AD biomarker signs in retinal microvasculature, even without clinical symptoms.
  • Differences in retinal microvasculature suggest potential utility as biomarkers across the AD spectrum.
  • Longitudinal studies are recommended to further elucidate the role of these retinal biomarkers in AD progression.