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- Title
Serum total TDP-43 levels are decreased in frontotemporal dementia patients with C9orf72 repeat expansion or concomitant motoneuron disease phenotype.
- Authors
Katisko, Kasper; Huber, Nadine; Kokkola, Tarja; Hartikainen, Päivi; Krüger, Johanna; Heikkinen, Anna-Leena; Paananen, Veera; Leinonen, Ville; Korhonen, Ville E.; Helisalmi, Seppo; Herukka, Sanna-Kaisa; Cantoni, Valentina; Gadola, Yasmine; Archetti, Silvana; Remes, Anne M.; Haapasalo, Annakaisa; Borroni, Barbara; Solje, Eino
- Abstract
Background: Frontotemporal 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. Methods: The 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. Results: Total 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. Conclusions: Our 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.
- Subjects
FRONTOTEMPORAL dementia; DEMENTIA patients; COMORBIDITY; DISEASE complications; BRAIN diseases; FRONTOTEMPORAL lobar degeneration
- Publication
Alzheimer's Research & Therapy, 2022, Vol 14, Issue 1, p1
- ISSN
1758-9193
- Publication type
Article
- DOI
10.1186/s13195-022-01091-8