Isoforms of Phosphorylated Tau as Potential Biomarkers for Alzheimer's Disease: The Contribution of Mass Spectrometry-Based Proteomics.

IF 1.6 Q3 CLINICAL NEUROLOGY
NeuroSci Pub Date : 2025-06-03 DOI:10.3390/neurosci6020050
Marco Agostini, Pietro Traldi, Mahmoud Hamdan
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Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, heterogeneous at the molecular level and characterized by diverse and complex pathological features. Such features are known to accumulate silently in the brain over years or even decades before the onset of detectable symptoms. Despite long years of intense research activities, the disease remains orphaned of either disease-modifying therapies or a specific blood test capable of predicting the disease in the pre-symptomatic stages. This disappointing outcome of such efforts can be attributed to a number of factors. One of these factors is the failure of earlier research to capture the heterogeneity of the disease. Such failure has the direct consequence of poor patient stratification, which in turn impacts negatively on the development of specific and effective therapy. The second factor is the absence of detailed and accurate information on proteins and associated post-translational modifications, which may influence the initiation and progress of the disease. Recent studies have demonstrated that the quantification of various isoforms of phosphorylated tau protein in plasma and other biofluids can be considered as potential biomarkers for the early detection of Alzheimer's disease. Mass spectrometry-based proteomics and immunoassay-based multiplex proteomics are the two technologies in current use for probing the human proteome, both in tissues and biofluids. In the present review, we discuss the contribution of MS-based proteomics to efforts aimed at the identification and eventual characterization of the heterogeneity of the disease, and the key role of the same technique in the analysis of protein post-translational modifications associated with the disease is also discussed.

磷酸化Tau亚型作为阿尔茨海默病的潜在生物标志物:基于质谱的蛋白质组学的贡献
阿尔茨海默病(AD)是一种进行性神经退行性疾病,在分子水平上具有异质性,具有多种复杂的病理特征。众所周知,这些特征在症状出现前几年甚至几十年就会在大脑中悄然积累。尽管进行了多年密集的研究活动,但这种疾病仍然缺乏改善疾病的治疗方法或能够在症状前阶段预测疾病的特定血液检查。这种努力的令人失望的结果可归因于若干因素。其中一个因素是早期的研究未能捕捉到这种疾病的异质性。这种失败的直接后果是患者分层不良,这反过来又对特异性和有效治疗的发展产生负面影响。第二个因素是缺乏关于蛋白质和相关翻译后修饰的详细和准确的信息,这可能影响疾病的发生和进展。最近的研究表明,血浆和其他生物体液中磷酸化tau蛋白的各种亚型的定量可以被认为是早期检测阿尔茨海默病的潜在生物标志物。基于质谱的蛋白质组学和基于免疫测定的多重蛋白质组学是目前用于探测组织和生物体液中人类蛋白质组的两种技术。在本综述中,我们讨论了基于ms的蛋白质组学对疾病异质性的鉴定和最终表征的贡献,并讨论了相同技术在分析与疾病相关的蛋白质翻译后修饰中的关键作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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