Inner retinal layer thickness reflects plasma biomarkers in preclinical Alzheimer’s disease

Purpose/background: Few studies have examined layer- and region-specific retinal thickness in relation to plasma Alzheimer's disease (AD) biomarkers in cognitively normal adults at increased risk for AD. We conducted an exploratory pilot study to examine whether thickness measurements of the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), and outer plexiform layer (OPL) were associated with plasma AD biomarkers. Methods: Spectral-domain optical coherence tomography was performed on 20 eyes from 11 cognitively normal participants enriched for AD risk using a low plasma Aβ42/40 ratio (<0.10). Retinal layers were segmented using a novel deep-learning algorithm, followed by manual review and refinement by trained graders when needed. Associations between retinal thickness and plasma neurofilament-light chain (NfL), glial fibrillary acidic protein (GFAP), Aβ42/40, p-tau217, and p-tau181 were evaluated using ridge regression with participant-level bootstrap resampling. Results: Exploratory relationships suggest that thinner INL and GCL measurements are associated with higher p-tau217 and GFAP levels. Conclusion: Larger, longitudinal studies with confirmatory AD biomarker characterization are needed to validate these preliminary findings to determine how retinal OCT adds complementary value to plasma biomarkers for early AD risk assessment.