ArticleAlzheimer's research & therapy2022
Serum total TDP-43 levels are decreased in frontotemporal dementia patients with C9orf72 repeat expansion or concomitant motoneuron disease phenotype.
Article in Alzheimer's research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- An acetylated Tau-174 CSF biomarker discriminates between TDP-43 and tau pathology in patients with frontotemporal lobar degeneration.Nature medicine · 2026Article
- Molecular signatures and biomarker development for limbic-predominant age-related TDP-43 encephalopathy (LATE).Acta neuropathologica · 2026Review
- TDP-43 proteinopathies and neurodegeneration: insights from Caenorhabditis elegans models.The FEBS journal · 2026Review
- Fluid biomarkers for neurodegenerative diseases: a comprehensive update.Alzheimer's research & therapy · 2025Review
- Glial and neuronal cell-free DNA in plasma of sporadic bvFTD and late onset primary psychiatric disease patients.Scientific reports · 2025Article
- Elevated TDP-43 serum levels associated with postoperative delirium following major cardiac surgery.Brain, behavior, & immunity - health · 2025Article
- TDP-43 seeding activity in the olfactory mucosa of patients with amyotrophic lateral sclerosis.Molecular neurodegeneration · 2025Article
- Context-dependent Interactors Regulate TDP-43 Dysfunction in ALS/FTLD.bioRxiv : the preprint server for biology · 2025Article
- Alzheimer's disease neuropathology and its estimation with fluid and imaging biomarkers.Molecular neurodegeneration · 2025Review
- Fluid biomarkers in familial frontotemporal dementia: progress and prospects.Frontiers in neurology · 2025Review
- TDP-43-proteinopathy at the crossroads of tauopathy: on copathology and current and prospective biomarkers.Frontiers in cellular neuroscience · 2025Review
- Development of a Sensitive and Reliable Meso Scale Discovery-Based Electrochemiluminescence Immunoassay to Quantify TDP-43 in Human Biofluids.Biosensors · 2024Article
- Blood-Based Biomarkers in Frontotemporal Dementia: A Narrative Review.International journal of molecular sciences · 2024Review
- Frequency and Longitudinal Course of Behavioral and Neuropsychiatric Symptoms in Participants With Genetic Frontotemporal Dementia.Neurology · 2024Article
- Blood-Based Biomarkers in Alzheimer's Disease: Advancing Non-Invasive Diagnostics and Prognostics.International journal of molecular sciences · 2024Review
- In vivo diagnosis of TDP-43 proteinopathies: in search of biomarkers of clinical use.Translational neurodegeneration · 2024Review
- Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS.Nature medicine · 2024Article
- Detection of TDP-43 seeding activity in the olfactory mucosa from patients with frontotemporal dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Review
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Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFrontotemporal dementia (FTD) covers a spectrum of neurodegenerative disorders with various clinical and neuropathological subtypes. The two major pathological proteins accumulating in the brains of FTD patients, depending on their genetic background, are TDP-43 and tau. We aimed to evaluate whether total TDP-43 levels measured from the serum associate with the genotype or clinical phenotype of the FTD patients and whether serum TDP-43 provides prognostic or diagnostic value in the FTD spectrum disorders.
methodsThe study cohort included 254 participants with a clinical diagnosis of FTD (including all major genotypes and clinical phenotypes) and 105 cognitively healthy controls. Serum total TDP-43 levels measured with a single-molecule array (Simoa) were compared within the FTD group according to the genotype, clinical phenotype, and predicted neuropathological subtype of the patients. We also evaluated the associations between the TDP-43 levels and disease severity or survival in FTD.
resultsTotal TDP-43 levels in the serum were significantly lower in the FTD group as compared to the healthy control group (275.3 pg/mL vs. 361.8 pg/mL, B = 0.181, 95%CI = 0.014-0.348, p = 0.034). The lowest TDP-43 levels were observed in the subgroup of FTD patients harboring predicted TDP-43 brain pathology (FTD-TDP, 241.4 pg/mL). The low levels in the FTD-TDP group were especially driven by C9orf72 repeat expansion carriers (169.2 pg/mL) and FTD patients with concomitant motoneuron disease (FTD-MND, 113.3 pg/mL), whereas GRN mutation carriers did not show decreased TDP-43 levels (328.6 pg/mL). Serum TDP-43 levels showed no correlation with disease severity nor progression in FTD.
conclusionsOur results indicate that the total levels of TDP-43 in the serum are decreased especially in FTD patients with the C9orf72 repeat expansion or FTD-MND phenotype, both subtypes strongly associated with TDP-43 type B brain pathology. Serum-based measurement of TDP-43 could represent a useful tool in indicating C9orf72 repeat expansion and FTD-MND-related TDP-43 neuropathology for future diagnostics and intervention studies.
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