Alzheimer's & Dementia · May 24, 2026

A fovea-centered retinal signature linked to plasma biomarkers in prodromal Alzheimer's disease

By Teijeira-Portas S, Murueta-Goyena A, Zamora-Otaola A et al.

INTRODUCTION: Blood biomarkers detect Alzheimer's disease (AD), but tissue correlates of early tau pathology and glial activation remain unclear. We investigated whether multimodal retinal measures capture a focal prodromal AD (pAD) pattern linked to plasma biomarkers. METHODS: Thirty-eight individuals with pAD and 40 controls underwent optical coherence tomography (OCT), OCT-angiography (OCT-A), and electroretinography (ERG). Plasma p-tau217, p-tau181, glial fibrillary acidic protein (GFAP) Aβ42 and Aβ40 were quantified, adjusting for age, sex, and vascular risk factors. RESULTS: Between-group differences were restricted to parafoveal OCT-A measures. Within the pAD group, higher p-tau217/Aβ42 and GFAP showed consistent associations with foveal measures: increased ganglion cell-inner plexiform layer (GCIPL) thickness, capillary density, altered foveal avascular zone (FAZ), and reduced photopic negative-response amplitude. These associations were absent in controls. Mediation analyses indicated that foveal GCIPL thickness largely accounted for blood biomarker-microvascular/ERG associations. DISCUSSION: pAD exhibits a spatially consistent, fovea-centered neurovascular and functional signature-tracking plasma tau phosphorylation and glial activation, supporting the fovea as a sensitive region in early disease-related processes.

doi.org/10.1002/dad2.70369Open accessPubMed 42255961Biomarkers