Biomarkers for Alzheimer's disease are upregulated in patients with diabetic retinopathy

Background Diabetes has been linked to increased prevalence of dementia, but the link between diabetic retinopathy (DR) and Alzheimer's disease (AD) remains unclear. Objective This study aimed to evaluate potential associations between DR and AD-related protein biomarkers in plasma and ocular fluid. Methods A prospective, cross-sectional study collected human blood, vitreous, aqueous, and tear samples and measured amyloid-β (Aβ 40 , Aβ 42 ), total-tau (t-tau), phosphorylated-tau (ptau181), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) by digital immunoassays. Results The study included 79 eyes (79 patients) [41 females (59.4%); mean (SD) age 57.1 (12.2) years] of which DR was present in 44 (55.7%). All six biomarkers were significantly higher in plasma in participants with DR compared to those without DR [Aβ 40 p = 0.002, Aβ 42 p = 0.002, t-tau = 0.013, ptau181 p = 0.005, GFAP p = 0.010, and NfL p < 0.001]. Within vitreous, DR participants had significantly elevated t-tau (p = 0.002), ptau181 (p = 0.049), and NfL (p = 0.006); and within aqueous, higher NfL (p = < 0.001). Neuropsychological testing scores were lower in participants with DR than those without but did not reach statistical significance (Montreal-Cognitive-Assessment: p = 0.070; Mini-Mental-State-Exam: p = 0.057). Conclusions This study showed significant increases of AD associated protein biomarkers in plasma, vitreous, and aqueous in patients with DR. These results support a potential biological link between DR and AD pathology and suggest that DR, which tends to occur in younger individuals, may be a predictive factor for AD.