Quantifying neuronal biomarkers in aqueous humor in individuals undergoing routine cataract surgery and correlating with age and cognition

• Published in: Alzheimer's & dementia Vol. 19; no. S2
• Main Authors: Robbins, Cason B, Wisely, C. Ellis, Singh, Pali P, Kim, Terry, Grewal, Dilraj S, Fekrat, Sharon
• Format: Journal Article
• Language: English
• Published: 01.06.2023
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1002/alz.063688

Background Plasma and cerebrospinal fluid (CSF) levels of neuronal biomarkers have been associated with Alzheimer’s disease (AD). The aqueous humor, which can be collected during routine cataract surgery, may have similar concentrations of neuronal biomarkers to CSF. Method This proof‐of‐concept study prospectively enrolled adults without a diagnosis of cognitive impairment undergoing cataract surgery at a tertiary academic medical center. Participants underwent Montreal Cognitive Assessment (MoCA blind version 7.1, “abnormal” < 18) at the time of study enrollment. Aqueous samples were collected during cataract surgery through a surgical paracentesis. Samples were analyzed using an ultrasensitive single‐molecule array (SiMoA). Assessed biomarkers included phosphorylated tau (pTau)‐181, amyloid‐beta (Aß)‐42, Aß‐40, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). Correlations were assessed using Spearman’s rank correlation (rho). Result Sixteen eyes of 16 patients (average MoCA 19.2) underwent aqueous sampling to assess pTau‐181 and 7 eyes of 7 separate patients (average MoCA 20.0) underwent aqueous and plasma sampling to assess Aß‐42, Aß‐40, NfL, and GFAP. Aqueous pTau‐181 increased with increasing age (rho = 0.67, p = 0.0046). No aqueous or plasma biomarkers were significantly correlated with MoCA scores (all p > 0.05). Aqueous and plasma levels of biomarkers were not significantly correlated. Conclusion Neuronal biomarkers are measurable in aqueous humor using SiMoA analysis; however, these biomarkers did not significantly correlate with MoCA scores in a cognitively normal population. Further study in individuals with a known diagnosis of Alzheimer’s disease or mild cognitive impairment is indicated.