Brain and retina in Alzheimer's disease: Pathological intersections and estimates from imaging

Recent studies have highlighted retinal optical coherence tomography (OCT) imaging as a promising biomarker for the early detection of Alzheimer's disease (AD). This review connects AD brain pathology - particularly amyloid beta (Aβ), tau, and vascular changes - with corresponding retinal changes. Evidence suggests that abnormal Aβ and tau deposits in the retina may reflect brain pathology, though their formation mechanisms remain unclear. Retinal vascular changes may also mirror brain pathology, with recent data emerging on other co-pathologies. Retinal thickness changes, especially in acetylcholine-producing layers, can differentiate AD from controls, although not in early AD; however, emerging high-resolution OCT techniques may enhance early detection. We find that correlations between retinal thickness and brain structures are often weak, and retinal vascular imaging shows promise in estimating cerebrovascular disease markers from retinal vascular changes. Novel imaging modalities (e.g., hyperspectral imaging) for detecting retinal Aβ deposits may improve early AD screening when combined with other biomarkers. HIGHLIGHTS: Retinal Aβ/tau is equivocal; peripheral retinal p-tau shows diagnostic promise. OCT retinal/choroid thickness diagnostic/prognostic AUC is small to medium. Hyperspectral imaging and electroretinography may aid early diagnosis. OCTA may differentiate MCI from controls, but preclinical studies are needed. The added value of retinal biomarkers for risk stratification remains uncertain.