通过特异性检测 tau、TDP-43 和 FUS 病理学,发现额颞叶变性患者体内废物小体(淀粉体)的增加。

IF 6.2 2区 医学 Q1 NEUROSCIENCES
Raquel Alsina, Marta Riba, Agnès Pérez-Millan, Sergi Borrego-Écija, Iban Aldecoa, Clara Romera, Mircea Balasa, Anna Antonell, Albert Lladó, Yaroslau Compta, Jaume Del Valle, Raquel Sánchez-Valle, Carme Pelegrí, Laura Molina-Porcel, Jordi Vilaplana
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引用次数: 0

摘要

废物小体(或淀粉体)是一种多聚糖体,随着年龄的增长和某些神经退行性疾病的发生而出现在人脑中,被认为在神经系统清洁机制中具有潜在的作用。尽管以前对几种神经退行性疾病进行过研究,但它们在额颞叶变性(FTLD)中的地位仍未得到探讨。我们的研究旨在描述三种主要前颞叶变性蛋白病中废物小体的特征,评估其频率、分布、蛋白检测以及与衰老或病程的关系。我们从124名尸检确诊的散发性FTLD患者(包括75名tau(FTLD-tau)患者、42名TAR DNA结合蛋白43(FTLD-TDP)患者和7名肉瘤融合蛋白(FTLD-FUS)患者)以及29名对照组受试者的不同脑区获得了废物体评分。以死亡年龄和性别为协变量,通过置换检验评估了不同FLTD患者每个脑区的废物组数量,并通过多元回归探讨了与死亡年龄和病程的关系。双重免疫荧光研究检测了废体中与FTLD有关的蛋白质变化。与对照组相比,FTLD 患者的废物集聚量更高,尤其是 FTLD-FUS 患者。与FTLD-TDP和对照组不同的是,FTLD-tau和FTLD-FUS患者的废物团积累并不随年龄增长而增加。在FTLD-tau和FTLD-FUS中,病程较短的病例似乎表现出较高的废物集数量,而FTLD-TDP则似乎随着疾病的进展而增加。免疫荧光研究显示,在一些FTLD-tau和FTLD-TDP患者中,分离出的废物团外围分别存在tau和磷酸化-TDP-43。在FTLD-FUS患者的较多废物小体中观察到FUS的中心包涵体。这些发现表明废物小体在FTLD中的作用,尤其是在FLTD-FUS的侵袭性较强的形式中。从脑脊液中的废物小体中检测这些蛋白质,尤其是FUS,可能是FTLD的潜在生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Increase in wasteosomes (corpora amylacea) in frontotemporal lobar degeneration with specific detection of tau, TDP-43 and FUS pathology.

Wasteosomes (or corpora amylacea) are polyglucosan bodies that appear in the human brain with aging and in some neurodegenerative diseases, and have been suggested to have a potential role in a nervous system cleaning mechanism. Despite previous studies in several neurodegenerative disorders, their status in frontotemporal lobar degeneration (FTLD) remains unexplored. Our study aims to characterize wasteosomes in the three primary FTLD proteinopathies, assessing frequency, distribution, protein detection, and association with aging or disease duration. Wasteosome scores were obtained in various brain regions from 124 post-mortem diagnosed sporadic FTLD patients, including 75 participants with tau (FTLD-tau), 42 with TAR DNA-binding protein 43 (FTLD-TDP), and 7 with Fused in Sarcoma (FTLD-FUS) proteinopathies, along with 29 control subjects. The wasteosome amount in each brain region for the different FLTD patients was assessed with a permutation test with age at death and sex as covariables, and multiple regressions explored associations with age at death and disease duration. Double immunofluorescence studies examined altered proteins linked to FTLD in wasteosomes. FTLD patients showed a higher accumulation of wasteosomes than control subjects, especially those with FTLD-FUS. Unlike FTLD-TDP and control subjects, wasteosome accumulation did not increase with age in FTLD-tau and FTLD-FUS. Cases with shorter disease duration in FTLD-tau and FTLD-FUS seemed to exhibit higher wasteosome quantities, whereas FTLD-TDP appeared to show an increase with disease progression. Immunofluorescence studies revealed the presence of tau and phosphorylated-TDP-43 in the periphery of isolated wasteosomes in some patients with FTLD-tau and FTLD-TDP, respectively. Central inclusions of FUS were observed in a higher number of wasteosomes in FTLD-FUS patients. These findings suggest a role of wasteosomes in FTLD, especially in the more aggressive forms of FLTD-FUS. Detecting these proteins, particularly FUS, in wasteosomes from cerebrospinal fluid could be a potential biomarker for FTLD.

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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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