ALZHEIMER’S RESEARCH & THERAPY

Subramanian ML, Vig V, Chung J, Fiorello MG, Xia W, Zetterberg H, Blennow K, Zetterberg M, Shareef F, Siegel NH, Ness S, Jun GR and Stein TD.

Alzheimer’s Research & Therapy. 2020;12:111.

Link to Article 

Abstract

Purpose : Detecting NfL in the eye may provide an additional means to detect neurodegenerative disease in an at-risk population. We investigated the presence of NfL in the vitreous humor and its associations with levels of Alzheimer’s Disease (AD) biomarkers such as amyloid beta (Aβ) and total and phosphorylated Tau (t-Tau and p-Tau) proteins and inflammatory proteins in eyes. We also further examined the associations of NfL with mini-mental state examination (MMSE) scores, apolipoprotein E (APOE) allele status, systemic and ophthalmic diseases.

Methods : This is a single site, multi-surgeon, prospective, cross-sectional cohort study. Undiluted vitreous humor samples were taken from patients undergoing vitrectomy surgery for vitreoretinal disease and without known systemic neurodegenerative disease. Single molecule array immunoassay was used on 77 subjects to quantitatively measure NfL protein levels. Linear regression was used to test associations of NfL proteins with Aβ and Tau levels, inflammatory cytokines and interleukins, MMSE scores, ophthalmic and systemic diseases, and APOE allele genotype. All the protein levels were analysed after log transformation, and the regression models were adjusted for age, sex and eye disease.

Results : NfL was identified in over 77.9% of our sample at 500 pg/mL or more. The NfL level was significantly associated with increased levels of Aβ₄₀ (p=7.7×10^-5), Aβ₄₂ (p=2.8×10^-4), and t-Tau (p=5.5×10^-7), but not with p-Tau₁₈₁ (p=0.53). NfL also had significant and positive correlations with inflammatory cytokines such as IL_1A (p=2.9×10^-2), IL_17A (p=2.7×10^-2) and vascular endothelial growth factors like Vegf_C (p=8.6×10^-6), Vegf_D (p=1.8×10^-2), see table 1. However, we did not observe significant association of NfL with MMSE scores and APOE alleles. Notably, the presence of NfL was not found to be associated with eye disease in this study.

Conclusions : NfL concentration in the vitreous humor correlated significantly with other proteins in the vitreous that have a known association with neurodegenerative diseases, while not being associated with eye disease. Further investigation of NfL in ocular fluids could inform us about the utility of this biomarker in the eye and its potential role in identifying neurodegeneration and disease progression.

This is a 2020 ARVO Annual Meeting abstract..