Journal Article

Neurodegenerative biomarkers in different chambers of the eye relative to plasma: an agreement validation study

Ness, Steven, Stein, Thor D., Xia, Weiming, Subramanian, Manju L., Aytan, Nurgul, Spurlock, Elizabeth E., Tripodis, Yorghos, Alosco, Michael L., Chen, Xuejing, Tuz-Zahra, Fatima, Alluri, Sreevardhan, Siegel, Nicole H., Sampani, Konstantina

2024

Overview

Background Protein biomarkers have been broadly investigated in cerebrospinal fluid and blood for the detection of neurodegenerative diseases, yet a clinically useful diagnostic test to detect early, pre-symptomatic Alzheimer’s disease (AD) remains elusive. We conducted this study to quantify Aβ40, Aβ42, total Tau (t-Tau), hyperphosphorylated Tau (ptau181), glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) in eye fluids relative to blood. Methods In this cross-sectional study we collected vitreous humor, aqueous humor, tear fluid and plasma in patients undergoing surgery for eye disease. All six biomarkers were quantitatively measured by digital immunoassay. Spearman and Bland–Altman correlation analyses were performed to assess the agreement of levels between ocular fluids and plasma. Results Seventy-nine adults underwent pars-plana vitrectomy in at least one eye. Of the 79, there were 77 vitreous, 67 blood, 56 tear fluid, and 51 aqueous samples. All six biomarkers were quantified in each bio-sample, except GFAP and NfL in tear fluid due to low sample volume. All six biomarkers were elevated in vitreous humor compared to plasma samples. T-Tau, ptau181, GFAP and NfL were higher in aqueous than in plasma, and t-Tau and ptau181 concentrations were higher in tear fluid than in plasma. Significant correlations were found between Aβ40 in plasma and tears (r = 0.5; p  = 0.019), t-Tau in plasma and vitreous (r = 0.4; p  = 0.004), NfL in plasma and vitreous (r = 0.3; p  = 0.006) and plasma and aqueous (r = 0.5; p  = 0.004). No significant associations were found for Aβ42, ptau181 and GFAP among ocular fluids relative to plasma. Bland–Altman analysis showed aqueous humor had the closest agreement to plasma across all biomarkers. Biomarker levels in ocular fluids revealed statistically significant associations between vitreous and aqueous for t-Tau (r = 0.5; p  = 0.001), GFAP (r = 0.6; p  < 0.001) and NfL (r = 0.7; p  < 0.001). Conclusion AD biomarkers are detectable in greater quantities in eye fluids than in plasma and show correlations with levels in plasma. Future studies are needed to assess the utility of ocular fluid biomarkers as diagnostic and prognostic markers for AD, especially in those at risk with eye disease.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Adult / Aged / Aged, 80 and over / Alzheimer’s disease / Amyloid beta / Amyloid beta-Peptides - blood / Amyloid beta-Peptides - cerebrospinal fluid / Amyloid beta-Peptides - metabolism / Aqueous humor / Aqueous Humor - chemistry / Aqueous Humor - metabolism / Biological markers / Biomarkers - blood / Biomedical and Life Sciences / Biomedicine / Blood proteins / Cross-Sectional Studies / Degeneration / Evaluation / Female / Geriatric Psychiatry / Geriatrics/Gerontology / Glial Fibrillary Acidic Protein - blood / Glial Fibrillary Acidic Protein - metabolism / Health aspects / Humans / Male / Middle Aged / Nervous system / Neurodegenerative Diseases - blood / Neurodegenerative Diseases - diagnosis / Neurodegenerative Diseases - metabolism / Neurofilament Proteins - blood / Neurofilament Proteins - cerebrospinal fluid / Neurology / Neurosciences / Peptide Fragments - blood / Peptide Fragments - cerebrospinal fluid / Tau / tau Proteins - blood / tau Proteins - cerebrospinal fluid / tau Proteins - metabolism / Tears / Tears - chemistry / Tears - metabolism / Vitreous Body - metabolism / Vitreous humor