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

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.