阿尔茨海默病与听力损失患者中神经病理学生物标志物与血脑屏障相关的临床特征及潜在机制
Clinical Features and Potential Mechanisms Relating Neuropathological Biomarkers and Blood-Brain Barrier in Patients With Alzheimer's Disease and Hearing Loss.
作者信息
Zhang Wei-Jiao, Li Dan-Ning, Lian Teng-Hong, Guo Peng, Zhang Ya-Nan, Li Jing-Hui, Guan Hui-Ying, He Ming-Yue, Zhang Wen-Jing, Zhang Wei-Jia, Luo Dong-Mei, Wang Xiao-Min, Zhang Wei
机构信息
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Center for Cognitive Neurology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
出版信息
Front Aging Neurosci. 2022 Jun 16;14:911028. doi: 10.3389/fnagi.2022.911028. eCollection 2022.
BACKGROUND
The aim of this study was to explore clinical features and potential mechanisms relating neuropathological biomarkers and blood-brain barrier (BBB) in Alzheimer's disease (AD) and hearing loss (HL).
MATERIALS AND METHODS
A total of 65 patients with AD were recruited and auditory function was assessed by threshold of pure tone audiometry (PTA). Patients were divided into AD with HL (AD-HL) and AD with no HL (AD-nHL) groups based on the standard of World Health Organization. Clinical symptoms were assessed by multiple rating scales. The levels of neuropathological biomarkers of β amyloid1-42 (Aβ) and multiple phosphorylated tau (P-tau), and BBB factors of matrix metalloproteinases (MMPs), receptor of advanced glycation end products, glial fibrillary acidic protein, and low-density lipoprotein receptor related protein 1 were measured.
RESULTS
(1) Compared with AD-nHL group, AD-HL group had significantly impaired overall cognitive function and cognitive domains of memory, language, attention, execution, and activities of daily living (ADL) reflected by the scores of rating scales ( < 0.05). PTA threshold was significantly correlated with the impairments of overall cognitive function and cognitive domains of memory and language, and ADL in patients with AD ( < 0.05). (2) P-tau (S199) level was significantly increased in CSF from AD-HL group ( < 0.05), and was significantly and positively correlated with PTA threshold in patients with AD. (3) MMP-3 level was significantly elevated in CSF from AD-HL group ( < 0.05), and was significantly and positively correlated with PTA threshold in patients with AD ( < 0.05). (4) In AD-HL group, P-tau (S199) level was significantly and positively correlated with the levels of MMP-2 and MMP-3 in CSF ( < 0.05).
CONCLUSION
AD-HL patients have severely compromised overall cognitive function, multiple cognitive domains, and ADL. The potential mechanisms of AD-HL involve elevations of AD neuropathological biomarker of P-tau (S199) and BBB factor of MMP-3, and close correlations between P-tau (S199) and MMP-2/MMP-3 in CSF. Findings from this investigation highly suggest significance of early evaluation of HL for delaying AD progression, and indicate new directions of drug development by inhibiting neuropathological biomarkers of AD and protecting BBB.
背景
本研究旨在探讨阿尔茨海默病（AD）与听力损失（HL）中神经病理学生物标志物和血脑屏障（BBB）相关的临床特征及潜在机制。
材料与方法
共招募65例AD患者，通过纯音听力计（PTA）阈值评估听觉功能。根据世界卫生组织标准，将患者分为伴有HL的AD（AD-HL）组和不伴有HL的AD（AD-nHL）组。通过多个评定量表评估临床症状。检测β淀粉样蛋白1-42（Aβ）和多种磷酸化tau蛋白（P-tau）的神经病理学生物标志物水平，以及基质金属蛋白酶（MMPs）、晚期糖基化终产物受体、胶质纤维酸性蛋白和低密度脂蛋白受体相关蛋白1的血脑屏障因子水平。
结果
（1）与AD-nHL组相比，AD-HL组在评定量表评分中显示出整体认知功能以及记忆、语言、注意力、执行能力和日常生活活动（ADL）等认知领域显著受损（<0.05）。AD患者的PTA阈值与整体认知功能、记忆和语言认知领域以及ADL的损害显著相关（<0.05）。（2）AD-HL组脑脊液中P-tau（S199）水平显著升高（<0.05），且与AD患者的PTA阈值显著正相关。（3）AD-HL组脑脊液中MMP-3水平显著升高（<0.05），且与AD患者的PTA阈值显著正相关（<0.05）。（4）在AD-HL组中，脑脊液中P-tau（S199）水平与MMP-2和MMP-3水平显著正相关（<0.05）。
结论
AD-HL患者的整体认知功能、多个认知领域和ADL严重受损。AD-HL的潜在机制包括AD神经病理学生物标志物P-tau（S199）和血脑屏障因子MMP-3升高，以及脑脊液中P-tau（S199）与MMP-2/MMP-3之间的密切相关性。本研究结果强烈提示早期评估HL对延缓AD进展的重要性，并为通过抑制AD神经病理学生物标志物和保护血脑屏障来开发新药指明了新方向。
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