INTRODUCTION: Retinal microvascular changes may reflect cerebral pathology in Alzheimer’s disease (AD), but their relationships with plasma biomarkers and neuroimaging remain underexplored.

 

METHODS: In this cross-sectional study, 55 AD and 55 controls underwent retinal imaging (color fundus photography [CFP] and optical coherence tomography angiography [OCTA]), brain MRI, amyloid PET, and plasma biomarker analysis. Associations between retinal metrics, plasma biomarkers (Aβ42/40, p-tau181, p-tau217, GFAP), neuroimaging (SUVR, centiloid, peak-width of skeletonized mean diffusivity (PSMD), White matter (WM)-free water), and cognitive performance were assessed.

 

RESULTS: Retinal changes in AD correlated with elevated amyloid (centiloid and SUVR, p < 0.05), plasma biomarkers (p-tau 181, p-tau 217, p-tau 217/Aß42), white matter damage (PSMD and WM-free water, p < 0.01), and poorer cognition (p < 0.001). Mediation analysis revealed centiloid and WM-free water partially mediated the retinal-cognitive relationship.

 

CONCLUSIONS: Retinal microvascular alterations are linked to AD pathology and cognitive decline, supporting their potential as non-invasive biomarkers.