Serum total TDP-43 levels are decreased in frontotemporal dementia patients with C9orf72 repeat expansion or concomitant motoneuron disease phenotype

• DOI: 10.1186/s13195-022-01091-8
• Publication Date: 2022-10-11T02:02:59Z
• Authors: Kasper Katisko; Nadine Huber; Tarja Kokkola; Päivi Hartikainen; Johanna Krüger; Anna-Leena Heikkinen; Veera Paananen; Ville Leinonen; Ville E. Korhonen; Seppo Helisalmi; Sanna-Kaisa Herukka; Valentina Cantoni; Yasmine Gadola; Silvana Archetti; Anne M. Remes; Annakaisa Haapasalo; Barbara Borroni; Eino Solje
• Keywords: C9ORF72; Concomitant; Geriatric psychiatry; Clinical phenotype

Frontotemporal dementia (FTD) covers a spectrum of neurodegenerative disorders with various clinical and neuropathological subtypes. The two major pathological proteins accumulating in the brains FTD patients, depending on their genetic background, are TDP-43 tau. We aimed to evaluate whether total levels measured from serum associate genotype or phenotype patients provides prognostic diagnostic value disorders. study cohort included 254 participants diagnosis (including all genotypes phenotypes) 105 cognitively healthy controls. Serum single-molecule array (Simoa) were compared within group according genotype, phenotype, predicted subtype patients. also evaluated associations between disease severity survival FTD. Total significantly lower as control (275.3 pg/mL vs. 361.8 pg/mL, B = 0.181, 95%CI 0.014-0.348, p 0.034). lowest observed subgroup harboring brain pathology (FTD-TDP, 241.4 pg/mL). low FTD-TDP especially driven by C9orf72 repeat expansion carriers (169.2 pg/mL) concomitant motoneuron (FTD-MND, 113.3 pg/mL), whereas GRN mutation did not show decreased (328.6 showed no correlation nor progression Our results indicate that FTD-MND both subtypes strongly associated type pathology. Serum-based measurement could represent useful tool indicating FTD-MND-related neuropathology for future diagnostics intervention studies.