散发性阿尔茨海默病(AD)患者成纤维细胞中线粒体的改变与 AD 相关临床特征相关。

IF 6.2 2区 医学 Q1 NEUROSCIENCES Acta Neuropathologica Communications Pub Date : 2024-06-08 DOI:10.1186/s40478-024-01807-x
Fanny Eysert, Paula-Fernanda Kinoshita, Julien Lagarde, Sandra Lacas-Gervais, Laura Xicota, Guillaume Dorothée, Michel Bottlaender, Frédéric Checler, Marie-Claude Potier, Marie Sarazin, Mounia Chami
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引用次数: 0

摘要

线粒体功能障碍是阿尔茨海默病(AD)的主要特征。关于这些障碍在阿尔茨海默病患者外周细胞中的发生情况及其与疾病进展的潜在相关性,我们的研究还不够深入。我们研究了健康志愿者和处于前驱期(AD-MCI)或痴呆期(AD-D)的阿氏症患者成纤维细胞的线粒体结构、功能和有丝分裂。我们进行了与临床认知评分的相关性研究,即(i) Mini-Mental State Examination (MMSE)和(ii) Dementia Rating-Scale Sum of Boxes (CDR-SOB),以及与(iii) amyloid beta (Aβ) plaque burden (PiB-PET imaging) 和(iv) peripheral amyloid precursor protein C-terminal fragments (APP-CTFs) 的相关性研究。我们揭示了AD-MCI和AD-D成纤维细胞线粒体结构的改变以及特定的线粒体功能障碍特征,并发现有丝分裂和自噬缺陷与AD-D成纤维细胞溶酶体活性受损有关。我们报告了这些功能障碍的一个子集与认知能力下降、AD 相关临床特征和外周 APP-CTFs 积累之间的重要相关性。这项研究强调了外周细胞在研究AD病理生理学方面的潜在用途。
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Mitochondrial alterations in fibroblasts from sporadic Alzheimer's disease (AD) patients correlate with AD-related clinical hallmarks.

Mitochondrial dysfunctions are key features of Alzheimer's disease (AD). The occurrence of these disturbances in the peripheral cells of AD patients and their potential correlation with disease progression are underinvestigated. We studied mitochondrial structure, function and mitophagy in fibroblasts from healthy volunteers and AD patients at the prodromal (AD-MCI) or demented (AD-D) stages. We carried out correlation studies with clinical cognitive scores, namely, (i) Mini-Mental State Examination (MMSE) and (ii) Dementia Rating-Scale Sum of Boxes (CDR-SOB), and with (iii) amyloid beta (Aβ) plaque burden (PiB-PET imaging) and (iv) the accumulation of peripheral amyloid precursor protein C-terminal fragments (APP-CTFs). We revealed alterations in mitochondrial structure as well as specific mitochondrial dysfunction signatures in AD-MCI and AD-D fibroblasts and revealed that defective mitophagy and autophagy are linked to impaired lysosomal activity in AD-D fibroblasts. We reported significant correlations of a subset of these dysfunctions with cognitive decline, AD-related clinical hallmarks and peripheral APP-CTFs accumulation. This study emphasizes the potential use of peripheral cells for investigating AD pathophysiology.

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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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