Alzheimer's Disease-Related Analytes Amyloid-β and Tau in Perilymph: Correlation With Patient Age and Cognitive Score

Abstract

Objective: To describe the collection methods for perilymph fluid biopsy during cochlear implantation, detect levels of amyloid β 42 and 40 (Aβ₄₂ and Aβ₄₀), and total tau (tTau) analytes with a high-precision assay, to compare these levels with patient age and Montreal Cognitive Assessment (MoCA) scores, and explore potential mechanisms and relationships with otic pathology.

Study design: Prospective study.

Setting: Tertiary referral center.

Methods: Perilymph was collected from 25 patients using polyimide tubing to avoid amyloid adherence to glass, and analyzed with a single-molecule array advanced digital enzyme-linked immunosorbent assay platform for Aβ₄₀, Aβ₄₂, and tTau. Cognition was assessed by MoCA.

Results: Perilymph volumes ranged from ∼1 to 13 µL, with analyte concentrations spanning 2.67 to 1088.26 pg/mL. All samples had detectable levels of tTau, Aβ₄₀, and Aβ₄₂, with a significant positive correlation between Aβ₄₂ and Aβ₄₀ levels. Levels of Aβ₄₂, Aβ₄₀, and tTau were positively correlated with age, while MoCA scores were inversely correlated with age. tTau and Aβ₄₂/Aβ₄₀-ratios were significantly correlated with MoCA scores.

Conclusion: Alzheimer's disease-associated peptides Aβ₄₂, Aβ₄₀, and tau analytes are detectable in human perilymph at levels approximately 10-fold lower than those found in cerebrospinal fluid (CSF). These species increase with age and correlate with cognitive impairment indicators, suggesting their potential utility as biomarkers for cognitive impairment in patients undergoing cochlear implantation. Future research should investigate the origin of these analytes in the perilymph and their potential links to inner ear pathologies and hearing loss, as well as their relationships to CSF and plasma levels in individuals.

Keywords: Alzheimer's disease; Aβ40; Aβ42; MoCA; amyloid; cochlear implantation; cognition; perilymph; tau.