Department of Neurology, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, 81675 Munich, Germany.
Department of Quantitative Biomedicine, University of Zurich, 8057 Zurich, Switzerland.
Cells. 2023 Feb 12;12(4):597. doi: 10.3390/cells12040597.
TDP-43 is the primary or secondary pathological hallmark of neurodegenerative diseases, such as amyotrophic lateral sclerosis, half of frontotemporal dementia cases, and limbic age-related TDP-43 encephalopathy, which clinically resembles Alzheimer's dementia. In such diseases, a biomarker that can detect TDP-43 proteinopathy in life would help to stratify patients according to their definite diagnosis of pathology, rather than in clinical subgroups of uncertain pathology. For therapies developed to target pathological proteins that cause the disease a biomarker to detect and track the underlying pathology would greatly enhance such undertakings. This article reviews the latest developments and outlooks of deriving TDP-43-specific biomarkers from the pathophysiological processes involved in the development of TDP-43 proteinopathy and studies using biosamples from clinical entities associated with TDP-43 pathology to investigate biomarker candidates.
TDP-43 是神经退行性疾病（如肌萎缩侧索硬化症、半数额颞叶痴呆病例和边缘性与年龄相关的 TDP-43 脑病）的主要或次要病理标志物，其临床表现类似于阿尔茨海默病。在这些疾病中，一种能够在生命中检测 TDP-43 蛋白病的生物标志物将有助于根据明确的病理诊断对患者进行分层，而不是根据临床亚组的不确定病理进行分层。对于针对导致疾病的病理蛋白的治疗方法，检测和跟踪潜在病理的生物标志物将极大地增强这些努力。本文综述了从 TDP-43 蛋白病发展过程中的病理生理过程中提取 TDP-43 特异性生物标志物的最新进展和展望，以及使用与 TDP-43 病理相关的临床实体的生物样本进行的研究，以调查生物标志物候选物。
