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

Author:

Walia Amit1ORCID,Shew Matthew A.1,Durakovic Nedim1,Herzog Jacques A.1,Cirrito John R.2,Yuede Carla M.2,Wick Cameron C.1,Manis Melissa2,Holtzman David M.23,Buchman Craig A.1,Rutherford Mark A.1

Affiliation:

1. Department of Otolaryngology–Head and Neck Surgery Washington University School of Medicine in St Louis St Louis Missouri USA

2. Department of Neurology Washington University School of Medicine in St Louis St Louis Missouri USA

3. Hope Center for Neurological Disorders Knight Alzheimer's Disease Research Center, Washington University in St. Louis St. Louis Missouri USA

Abstract

AbstractObjectiveTo 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 DesignProspective study.SettingTertiary referral center.MethodsPerilymph 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.ResultsPerilymph 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.ConclusionAlzheimer'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.

Publisher

Wiley

Reference57 articles.

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