Vitreous Humor Biomarkers Reflect Pathological Changes in the Brain for Alzheimer's Disease and Chronic Traumatic Encephalopathy

Background: Patients with eye disease have an increased risk for developing neurodegenerative disease. Neurodegenerative proteins can be measured in the eye; however, correlations between biomarker levels in eye fluid and neuropathological diagnoses have not been established. Objective: This exploratory, retrospective study examined vitreous humor from 41 postmortem eyes and brain tissue with neuropathological diagnoses of Alzheimer's disease (AD, n = 7), chronic traumatic encephalopathy (CTE, n = 15), both AD + CTE (n = 10), and without significant neuropathology (controls, n = 9). Methods: Protein biomarkers i.e., amyloid-beta (A beta(40,42)), total tau (tTau), phosphorylated tau (pTau(181,231)), neurofilament light chain (NfL), and eotaxin-1 were quantitatively measured by immunoassay. Non-parametric tests were used to compare vitreous biomarker levels between groups. Spearman's rank correlation tests were used to correlate biomarker levels in vitreous and cortical tissue. The level of significance was set to alpha = 0.10. Results: In pairwise comparisons, tTau levels were significantly increased in AD and CTE groups versus controls (p = 0.08 for both) as well asADversus AD+CTE group and CTE versus AD+CTE group (p = 0.049 for both). Vitreous NfL levels were significantly increased in low CTE (Stage I/II) versus no CTE (p = 0.096) and in low CTE versus high CTE stage (p = 0.03). Vitreous and cortical tissue levels of pTau(231) (p = 0.02, r = 0.38) and t-Tau (p = 0.04, r = -0.34) were significantly correlated. Conclusion: The postmortem vitreous humor biomarker levels significantly correlate with AD and CTE pathology in corresponding brains, while vitreous NfL was correlated with the CTE staging. This exploratory study indicates that biomarkers in the vitreous humor may serve as a proxy for neuropathological disease.