Movement disorders are linked to TDP-43 burden in the substantia nigra of FTLD-TDP brain donors.

IF 6.2 2区 医学 Q1 NEUROSCIENCES
Luigi Fiondella, Priya Gami-Patel, Christian A Blok, Annemieke J M Rozemuller, Jeroen J M Hoozemans, Yolande A L Pijnenburg, Marta Scarioni, Anke A Dijkstra
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引用次数: 1

Abstract

Movement disorders (MD) have been linked to degeneration of the substantia nigra (SN) in Parkinson's disease and include bradykinesia, rigidity, and tremor. They are also present in frontotemporal dementia (FTD), where MD have been linked to frontotemporal lobar degeneration with tau pathology (FTLD-tau). Although MD can also occur in FTLD with TDP-43 pathology (FTLD-TDP), the local pathology in the SN of FTLD-TDP patients with MD is currently unexplored. The aims of this study are to characterize the frequency and the nature of MD in a cohort of FTLD-TDP brain donors and to investigate the relationship between the presence of MD, the nigral neuronal loss, and the TDP-43 burden in the SN. From our cohort of FTLD-TDP patients (n = 53), we included 13 donors who presented with MD (FTLD-MD+), and nine age-sex matched donors without MD (FTLD-MD-) for whom the SN was available. In these donors, the TDP-43 burden and the neuronal density in the SN were assessed with ImageJ and Qupath software. The results were compared between the two groups using T-test. We found that the TDP-43 burden in the SN was higher in FTLD-MD+ (mean 3,43%, SD ± 2,7) compared to FTLD-MD- (mean 1,21%, SD ± 0,67) (p = 0,04), while no significant difference in nigral neuronal density was found between the groups (p = 0,09). 17% of FTLD-TDP patients developed MD, which present as symmetric akinetic-rigid parkinsonism or CBS. Given the absence of a significant nigral neuronal cell loss, TDP-43 induced neuronal dysfunction could be sufficient to cause MD.

运动障碍与FTLD-TDP脑供者黑质中TDP-43负荷有关。
运动障碍(MD)与帕金森病的黑质(SN)变性有关,包括运动迟缓、强直和震颤。它们也存在于额颞叶痴呆(FTD)中,其中MD与伴有tau病理学的额颞叶变性(FTLD-tau)有关。虽然伴有TDP-43病理的FTLD也可发生MD (FTLD- tdp),但FTLD- tdp患者SN的局部病理目前尚不清楚。本研究的目的是表征FTLD-TDP脑供者队列中MD的频率和性质,并研究MD的存在、神经神经元丢失和SN中TDP-43负担之间的关系。从我们的FTLD-TDP患者队列(n = 53)中,我们包括13名出现MD (FTLD-MD+)的供者,以及9名年龄性别匹配的无MD (FTLD-MD-)的供者,他们的SN可用。应用ImageJ和Qupath软件对这些供体的TDP-43负荷和SN内的神经元密度进行评估。两组间比较采用t检验。我们发现,与FTLD-MD-(平均1.21%,SD±0.67)相比,FTLD-MD+组SN中的TDP-43负荷(平均3.43%,SD±2.7)更高(p = 0.04),而两组之间的神经细胞密度无显著差异(p = 0.09)。17%的FTLD-TDP患者发展为MD,表现为对称性动刚性帕金森病或CBS。鉴于没有显著的神经神经元细胞损失,TDP-43诱导的神经元功能障碍可能足以导致MD。
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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来源期刊
Acta Neuropathologica Communications
Acta Neuropathologica Communications Medicine-Pathology and Forensic Medicine
CiteScore
11.20
自引率
2.80%
发文量
162
审稿时长
8 weeks
期刊介绍: "Acta Neuropathologica Communications (ANC)" is a peer-reviewed journal that specializes in the rapid publication of research articles focused on the mechanisms underlying neurological diseases. The journal emphasizes the use of molecular, cellular, and morphological techniques applied to experimental or human tissues to investigate the pathogenesis of neurological disorders. ANC is committed to a fast-track publication process, aiming to publish accepted manuscripts within two months of submission. This expedited timeline is designed to ensure that the latest findings in neuroscience and pathology are disseminated quickly to the scientific community, fostering rapid advancements in the field of neurology and neuroscience. The journal's focus on cutting-edge research and its swift publication schedule make it a valuable resource for researchers, clinicians, and other professionals interested in the study and treatment of neurological conditions.
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