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耳淋巴液中与阿尔茨海默病相关的分析物β淀粉样蛋白和tau:与患者年龄和认知评分的相关性。

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

机构信息

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

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

出版信息

Otolaryngol Head Neck Surg. 2024 Dec;171(6):1850-1858. doi: 10.1002/ohn.942. Epub 2024 Aug 27.

Abstract

OBJECTIVE

To describe the collection methods for perilymph fluid biopsy during cochlear implantation, detect levels of amyloid β 42 and 40 (Aβ and Aβ), 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 Aβ, Aβ, 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, Aβ, and Aβ, with a significant positive correlation between Aβ and Aβ levels. Levels of Aβ, Aβ, and tTau were positively correlated with age, while MoCA scores were inversely correlated with age. tTau and Aβ/Aβ-ratios were significantly correlated with MoCA scores.

CONCLUSION

Alzheimer's disease-associated peptides Aβ, Aβ, 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.

摘要

目的

描述耳蜗植入术中收集外淋巴液活检样本的方法,使用高精度检测方法检测淀粉样蛋白 β42 和 40(Aβ 和 Aβ)以及总 tau(tTau)分析物的水平,比较这些水平与患者年龄和蒙特利尔认知评估(MoCA)评分的关系,并探讨与耳科病理相关的潜在机制和关系。

研究设计

前瞻性研究。

设置

三级转诊中心。

方法

使用聚酰亚胺管收集 25 例患者的外淋巴液,以避免淀粉样蛋白附着在玻璃上,并使用单分子阵列先进数字酶联免疫吸附测定平台分析 Aβ、Aβ 和 tTau。采用 MoCA 评估认知。

结果

外淋巴液量范围为 113μL,分析物浓度范围为 2.671088.26pg/mL。所有样本均检测到 tTau、Aβ 和 Aβ 的水平,且 Aβ 与 Aβ 水平之间存在显著的正相关关系。Aβ、Aβ 和 tTau 的水平与年龄呈正相关,而 MoCA 评分与年龄呈负相关。tTau 和 Aβ/Aβ 比值与 MoCA 评分显著相关。

结论

在人类外淋巴液中可以检测到阿尔茨海默病相关肽 Aβ、Aβ 和 tau 分析物,其水平约为脑脊液(CSF)中的 10 倍。这些物质随年龄增长而增加,并与认知障碍指标相关,提示它们在外淋巴液中的潜在用途作为接受耳蜗植入患者认知障碍的生物标志物。未来的研究应调查这些分析物在外淋巴液中的来源及其与内耳病理和听力损失的潜在联系,以及它们与个体 CSF 和血浆水平的关系。

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