Abstract
Purpose :
The eye provides a direct window to display neuro-retinal disease and the interconnections between the eye and brain may elucidate common features of both neurological and eye diseases. This exploratory, validation clinical study sought to examine vitreous levels of neurodegeneration biomarkers in postmortem eyes and brains of those with Alzheimer’s Disease (AD), Chronic Traumatic Encephalopathy (CTE), other tauopathies, and healthy controls.
Methods :
We examined 43 donated postmortem eyes and corresponding brains, with the diagnosis of AD, CTE, both AD + CTE, other tauopathies, and healthy controls by Meso Scale Discovery immunoassay to quantitatively measure amyloid-beta (Aβ), total and phosphorylated tau (tTau, pTau), neurofilament light chain (NfL), and eotaxin-1. Kruskall-Wallis Rank sum test and Wilcoxon rank tests were used to determine if vitreous biomarker levels were significantly associated with pathological diagnosis, ADNC, and CTE Staging. Spearman’s rank correlation was used to compare biomarker levels in vitreous and cortical tissue.
Results :
Vitreous levels of tTau (p=1.6x10-2), pTau-181 (p=6.4x10-3), and pTau-231 (p=4.2x10-2) were significantly associated with pathological brain diagnoses. In pairwise comparisons, significance was found for tTau in AD+CTE (n=9) vs CTE (n=15) (p=4.8x10-2) and AD+CTE vs AD (n=7) (p=4.8x10-2). NfL (p=1.7x10-2, n=33) in the vitreous was significantly associated with CTE Staging. When comparing vitreous levels to corresponding levels of the same biomarkers in cortical tissue, eotaxin-1 (p=1.3x10-2, n=32, r=-0.45) and t-Tau (p=1.0x10-4, n= 39, r=0.61) were significantly correlated.
Conclusions :
Vitreous tTau, pTau-181, and pTau-231 in postmortem eyes significantly correlate with AD and CTE pathology in post-mortem brains, while vitreous NfL was correlated with CTE staging. Additionally, vitreous and cortical tissue levels of tTau and eotaxin-1 were significantly correlated. This study validates prior reports by our group and lends further credence that the eye may serve as a potential source of diagnosis and prognosis of neurodegenerative diseases.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.