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阿尔茨海默病及其他疾病中 tau 和淀粉样蛋白-β 蛋白病变的影像学研究。

Imaging tau and amyloid-β proteinopathies in Alzheimer disease and other conditions.

机构信息

Department of Molecular Imaging and Therapy, Centre for PET, Austin Health, Heidelberg, Victoria, Australia.

Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.

出版信息

Nat Rev Neurol. 2018 Apr;14(4):225-236. doi: 10.1038/nrneurol.2018.9. Epub 2018 Feb 16.

Abstract

Most neurodegenerative disorders are associated with aggregated protein deposits. In the case of Alzheimer disease (AD), extracellular amyloid-β (Aβ) aggregates and intracellular tau neurofibrillary tangles are the two neuropathological hallmarks of the disease. Aβ-PET imaging has already been approved for clinical use and is being used in clinical trials of anti-Aβ therapies both for patient recruitment and as an outcome measure. These studies have shown that Aβ accumulation is a protracted process that can extend for more than 2 decades before the onset of clinical AD. This Review describes how in vivo brain imaging of Aβ pathology has revolutionized the evaluation of patients with clinical AD by providing robust and reproducible statements of global or regional brain Aβ burden and enabling the monitoring of disease progression. The role of selective tau imaging is discussed, focusing on how longitudinal tau and Aβ imaging studies might reveal the various effects (sequential and/or parallel, independent and/or synergistic) of these proteins on progression, cognition and other disease-specific biomarkers of neurodegeneration. Finally, imaging studies are discussed in the context of elucidating the respective roles of Aβ and tau in AD and in advancing our understanding of the relationship and/or interplay between these two proteinopathies.

摘要

大多数神经退行性疾病都与聚集的蛋白质沉积有关。在阿尔茨海默病(AD)的情况下,细胞外淀粉样蛋白-β(Aβ)聚集体和细胞内 tau 神经原纤维缠结是该疾病的两个神经病理学标志。Aβ-PET 成像已获得临床批准,并正在 AD 患者的抗 Aβ 治疗临床试验中用于患者招募和作为疗效衡量指标。这些研究表明,Aβ 积累是一个漫长的过程,在临床 AD 发病前可以持续 20 多年。这篇综述描述了 Aβ 病理学的体内脑成像如何通过提供可靠和可重复的大脑 Aβ 负荷的全局或区域陈述以及能够监测疾病进展,彻底改变了对有临床 AD 患者的评估。还讨论了选择性 tau 成像的作用,重点是纵向 tau 和 Aβ 成像研究如何揭示这些蛋白质对进展、认知和其他神经退行性变的特定生物标志物的各种影响(顺序和/或并行、独立和/或协同)。最后,讨论了成像研究在阐明 Aβ 和 tau 在 AD 中的各自作用以及加深我们对这两种蛋白病之间的关系和/或相互作用的理解方面的作用。

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