Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
Department of Otolaryngology, Smell and Taste Center, Beijing Anzhen Hospital, Capital Medical University, YaBao Road 2, Beijing, 100029, Chaoyang District, China.
Eur Arch Otorhinolaryngol. 2022 Jul;279(7):3467-3476. doi: 10.1007/s00405-021-07143-3. Epub 2021 Oct 24.
Exosomal Phospho-Tau-181(P-T181-tau), Total tau (T-tau), and amyloid-β peptide 42 (Aβ42) have been proved the capacity for the amnestic mild cognitive impairment (MCI) and the diagnosis of Alzheimer's disease (AD). This study aimed to explore the cognitive function and the levels of P-T181-tau, T-tau, and Aβ42 in neuronal-derived exosomes (NDEs) extracted from plasma in normal cognitive adults over 45 years old with olfactory dysfunction.
A cross-sectional survey of 29 participants aged over 45 was conducted. Plasma exosomes were isolated, precipitated, and enriched by immuno-absorption with anti- L1 cell adhesion molecule (L1CAM) antibody. NDEs were characterized by CD81, and extracted NDE protein (P-T181-tau, T-tau, and Aβ42) biomarkers were quantified by enzyme-linked immunosorbent assay (ELISAs). Olfactory performance was assessed by Sniffin' Sticks and cognitive performance was assessed by Montreal Cognitive Assessment (MoCA).
There was no significant difference between adults with olfactory dysfunction and without olfactory dysfunction regarding the cognitive function as measured by MoCA and all the participants showed normal cognition. Adults with olfactory dysfunction showed a higher concentration of P-T181-tau in plasma NDEs than did adults without olfactory dysfunction (P = 0.034). Both the levels of P-T181-tau (r = - 0.553, P = 0.003) and T-tau (r = - 0.417, P = 0.034) negatively correlated with the odor identification scores. In addition, the level of T-tau negatively correlated with MoCA scores (r = - 0.597, P = 0.002). The levels of P-T181-tau (r = - 0.464, P = 0.022) and T-tau (r = - 0.438, P = 0.032) negatively correlated with the delayed recall scores.
This study demonstrated that cognition-related pathogenic proteins including P-T181-tau in plasma NDEs were significantly increased in adults over 45 years old with olfactory dysfunction before the occurrence of cognitive impairment. The impaired odor identification and the delayed recall function were highly associated with the increased levels of P-T181-tau and T-tau in plasma NDEs.
外泌体磷酸化 tau-181（P-T181-tau）、总 tau（T-tau）和淀粉样 β 肽 42（Aβ42）已被证明对遗忘型轻度认知障碍（MCI）和阿尔茨海默病（AD）具有诊断能力。本研究旨在探索认知功能以及 45 岁以上嗅觉功能障碍的正常认知成年人血浆中神经元衍生外泌体（NDE）中 P-T181-tau、T-tau 和 Aβ42 的水平。
对 29 名 45 岁以上的参与者进行了横断面调查。采用抗 L1 细胞黏附分子（L1CAM）抗体免疫吸附法分离、沉淀和富集血浆外泌体。通过 CD81 对 NDE 进行特征分析，并通过酶联免疫吸附测定（ELISA）定量提取的 NDE 蛋白（P-T181-tau、T-tau 和 Aβ42）生物标志物。使用 Sniffin' Sticks 评估嗅觉功能，使用蒙特利尔认知评估（MoCA）评估认知功能。
在 MoCA 评估的认知功能方面，有嗅觉功能障碍的成年人与无嗅觉功能障碍的成年人之间没有差异，所有参与者的认知均正常。有嗅觉功能障碍的成年人血浆 NDE 中的 P-T181-tau 浓度高于无嗅觉功能障碍的成年人（P=0.034）。P-T181-tau（r=-0.553，P=0.003）和 T-tau（r=-0.417，P=0.034）水平与嗅觉识别评分呈负相关。此外，T-tau 水平与 MoCA 评分呈负相关（r=-0.597，P=0.002）。P-T181-tau（r=-0.464，P=0.022）和 T-tau（r=-0.438，P=0.032）水平与延迟回忆评分呈负相关。
本研究表明，在认知障碍发生之前，45 岁以上有嗅觉功能障碍的成年人血浆 NDE 中包括 P-T181-tau 在内的与认知相关的致病蛋白显著增加。嗅觉识别受损和延迟回忆功能与血浆 NDE 中 P-T181-tau 和 T-tau 水平升高密切相关。
