Abstract
Purpose :
A method for diagnosis of early, pre-symptomatic Alzheimer’s Disease (AD), when therapies have the greatest effect, has not yet been realized. Protein biomarkers such as Aβ40, Aβ42, total Tau (t-Tau), phosphorylated Tau (p-Tau181), and neurofilament-light chain NfL are being investigated in blood and cerebrospinal fluid (CSF), and recent studies have reported on presence and utility of these markers in eye fluid. This study measured relative concentrations of biomarkers in eye-fluid biosamples from vitreous, aqueous, tears fluid, and blood within the same cohort of patients.
Methods :
In this single-site, cross-sectional study, patients underwent vitrectomy for eye disease and consented to collection of vitreous humor, aqueous humor, tear fluid, and blood. All five biomarkers were measured by digital immunoassay, and biomarker levels from all biosample sources were quantified. Spearman correlation analysis was performed to evaluate the agreement and validation of ocular biomarkers with reference to blood.
Results :
In total, 79 adults underwent pars-plana vitrectomy in at least one eye. All five biomarkers were tested in every biosample except for NfL in tear fluid, due to low sample volume (see table). Vitreous fluid had higher concentrations of all 5 biomarkers relative to blood, while t-Tau, p-Tau181 and NfL levels were higher in aqueous than blood, and t-Tau and p-Tau181 levels were higher in tears than blood. In correlation analysis, levels of Aβ40 in blood and tears were significantly correlated (r=0.495; p=0.019). T-Tau demonstrated positive significant correlations between blood and vitreous (r=0.356; p=0.004) and vitreous and aqueous (r=0.465; p=0.001). Significant correlations were also detected for NfL levels between blood and vitreous (r=0.334; p=0.006), blood and aqueous (r=0.490; p=0.004), and vitreous and aqueous (r=0.677; p<0.001). No significant association found in the different fluid sources for Aβ42 and p-Tau181 levels.
Conclusions :
This study found detectable levels of Aβ40, Aβ42, t-Tau, and p-Tau181 in vitreous, aqueous and tear fluid, relative to blood levels, in the same cohort. Levels of Aβ40, t-Tau, and NfL had significant correlations comparing different eye fluid sources to each other as well as to blood. Further studies are needed to validate our findings by correlating eye fluid biomarker levels to cognitive functioning and pre-symptomatic pathological changes in the brain with neuroimaging.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.