TDP-43 seeding activity in the olfactory mucosa of patients with amyotrophic lateral sclerosis
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Le résumé fourni par la source
BACKGROUND: In recent years, the seed amplification assay (SAA) has enabled the identification of pathological TDP-43 in the cerebrospinal fluid (CSF) and olfactory mucosa (OM) of patients with genetic forms of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we investigated the seeding activity of TDP-43 in OM samples collected from patients with sporadic ALS. METHODS: + SQSTM1 (n = 1), OPTN (n = 1), GLE1 (n = 1), FUS (n = 1) and SOD1 (n = 4) mutations; (c) other neurodegenerative disorders (OND), including Alzheimer's disease (n = 3), dementia with Lewy bodies (n = 8) and multiple system atrophy (n = 6); and (d) control subjects (n = 22). All samples were subjected to SAA analysis for TDP-43 (TDP-43_SAA). Plasmatic levels of TDP-43 and neurofilament-light chain (NfL) were also assessed in a selected number of patients. RESULTS: TDP-43_SAA was positive in 29/65 patients with sporadic MND, 9/21 patients with genetic MND, 6/17 OND patients and 3/22 controls. Surprisingly, one presymptomatic individual also tested positive. As expected, OM of genetic non-TDP-43-related MND tested negative. Interestingly, fluorescence values from non-MND samples that tested positive were consistently and significantly lower than those obtained with sporadic and genetic MND. Furthermore, among TDP-43-positive samples, the lag phase observed in MND patients was significantly longer than that in non-MND patients. Plasma TDP-43 levels were significantly higher in sporadic MND patients compared to controls and decreased as the disease progressed. Similarly, plasma NfL levels were higher in both sporadic and genetic MND patients and positively correlated with disease progression rate (ΔFS). No significant correlations were detected between TDP-43_SAA findings and the biological, clinical, or neuropsychological parameters considered. CONCLUSIONS: The OM of a subset of patients with sporadic MND can trigger seeding activity for TDP-43, as previously observed in genetic MND. Thus, TDP-43_SAA analysis of OM can improve the clinical characterization of ALS across different phenotypes and enhance our understanding of these diseases. Finally, plasma TDP-43 could serve as a potential biomarker for monitoring disease progression. However, further research is needed to confirm and expand these findings.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- TDP-43 seeding activity in the olfactory mucosa of patients with amyotrophic lateral sclerosis
- Date Crossref
- 26/04/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Milan Department of Pharmacological and Biomolecular Sciences pays non établi dans la noticeUniversité ou école supérieure
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Fondazione IRCCS Istituto Neurologico Carlo Besta pays non établi dans la noticeÉtablissement de santé
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Scuola Internazionale Superiore di Studi Avanzati pays non établi dans la noticeUniversité ou école supérieure
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AOL (United States) pays non établi dans la noticeEntreprise
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Ospedale San Paolo pays non établi dans la noticeÉtablissement de santé
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University of Verona Department of Neurosciences pays non établi dans la noticeUniversité ou école supérieure
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Unit of Neurology 3 - Neuroalgology and Motor Neuron Disease Centre pays non établi dans la noticeInstitution
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Unit of Neurology 5 - Neuropathology pays non établi dans la noticeInstitution
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Neuroradiology Unit pays non établi dans la noticeInstitution
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Laboratory of Prion Biology pays non établi dans la noticeStructure de recherche
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Unit of Laboratory Medicine pays non établi dans la noticeStructure de recherche
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Unit of Neurology 1 - Parkinson and Movement Disorders pays non établi dans la noticeInstitution
Department of Pharmacological and Biomolecular Sciences — University of Milan, Fondazione IRCCS Istituto Neurologico Carlo Besta et Scuola Internazionale Superiore di Studi Avanzati, avec 9 autres affiliations.
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