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蛋白质组学标志物与阿尔茨海默病的早期预测

Proteomic Markers and Early Prediction of Alzheimer's Disease.

作者信息

Zakharova Natalia V, Bugrova Anna E, Indeykina Maria I, Fedorova Yana B, Kolykhalov Igor V, Gavrilova Svetlana I, Nikolaev Evgeny N, Kononikhin Alexey S

机构信息

Emanuel Institute for Biochemical Physics, Russian Academy of Sciences, Moscow, 119334, Russia.

Mental Health Research Center, Moscow, 115522, Russia.

出版信息

Biochemistry (Mosc). 2022 Aug;87(8):762-776. doi: 10.1134/S0006297922080089.

Abstract

Alzheimer's disease (AD) is the most common socially significant neurodegenerative pathology, which currently affects more than 30 million elderly people worldwide. Since the number of patients grows every year and may exceed 115 million by 2050, and due to the lack of effective therapies, early prediction of AD remains a global challenge, solution of which can contribute to the timely appointment of a preventive therapy in order to avoid irreversible changes in the brain. To date, clinical assays for the markers of amyloidosis in cerebrospinal fluid (CSF) have been developed, which, in conjunction with the brain MRI and PET studies, are used either to confirm the diagnosis based on obligate clinical criteria or to predict the risk of AD developing at the stage of mild cognitive impairment (MCI). However, the problem of predicting AD at the asymptomatic stage remains unresolved. In this regard, the search for new protein markers and studies of proteomic changes in CSF and blood plasma are of particular interest and may consequentially identify particular pathways involved in the pathogenesis of AD. Studies of specific proteomic changes in blood plasma deserve special attention and are of increasing interest due to the much less invasive method of sample collection as compared to CSF, which is important when choosing the object for large-scale screening. This review briefly summarizes the current knowledge on proteomic markers of AD and considers the prospects of developing reliable methods for early identification of AD risk factors based on the proteomic profile.

摘要

阿尔茨海默病(AD)是最常见且具有重大社会意义的神经退行性病变,目前全球有超过3000万老年人受其影响。由于患者数量逐年增加,到2050年可能超过1.15亿,且缺乏有效的治疗方法,AD的早期预测仍然是一项全球性挑战,解决这一挑战有助于及时安排预防性治疗,以避免大脑发生不可逆转的变化。迄今为止,已经开发出针对脑脊液(CSF)中淀粉样变标志物的临床检测方法,这些方法与脑部MRI和PET研究相结合,要么用于根据严格的临床标准确诊,要么用于预测轻度认知障碍(MCI)阶段AD发生的风险。然而,无症状阶段AD的预测问题仍未解决。在这方面,寻找新的蛋白质标志物以及研究CSF和血浆中的蛋白质组变化尤为重要,这可能会确定AD发病机制中涉及的特定途径。与CSF相比,血浆中特定蛋白质组变化的研究值得特别关注,并且由于样本采集方法的侵入性小得多,在选择大规模筛查对象时这一点很重要,因此越来越受到关注。本综述简要总结了目前关于AD蛋白质组学标志物的知识,并探讨了基于蛋白质组学特征开发可靠的AD风险因素早期识别方法的前景。

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