Katisko, K., Huber, N., Kokkola, T. et al. Serum total TDP-43 levels are decreased in frontotemporal dementia patients with C9orf72 repeat expansion or concomitant motoneuron disease phenotype. Alz Res Therapy 14, 151 (2022). https://doi.org/10.1186/s13195-022-01091-8
Serum total TDP-43 levels are decreased in frontotemporal dementia patients with C9orf72 repeat expansion or concomitant motoneuron disease phenotype
|Author:||Katisko, Kasper1; Huber, Nadine2; Kokkola, Tarja1;|
1Institute of Clinical Medicine – Neurology, University of Eastern Finland, P.O. Box 1627 (Yliopistonranta 1C), FI-70211, Kuopio, Finland
2A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
3Neuro center, Neurology, Kuopio University Hospital, Kuopio, Finland
4Research Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland
5MRC, Oulu University Hospital, Oulu, Finland
6Neurology, Neurocenter, Oulu University Hospital, Oulu, Finland
7Finnish Institute of Occupational Health, Work Ability and Working Careers, Helsinki, Finland
8Neuro Center, Neurosurgery, Kuopio University Hospital, 70029, Kuopio, Finland
9Institute of Clinical Medicine – Neurosurgery, University of Eastern Finland, 70211, Kuopio, Finland
10Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland
11Centre for Neurodegenerative Disorders, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
12ASST Spedali Civili, Brescia, Italy
13Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland
14Medical Research Center, Oulu University Hospital, Oulu, Finland
|Online Access:||PDF Full Text (PDF, 1 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2023030129065
|Publish Date:|| 2023-03-01
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.
Alzheimers research & therapy
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
3124 Neurology and psychiatry
This study has received funding from the Finnish Medical Foundation (KK, no grant number), the Finnish-Norwegian Medical Foundation (KK, no grant number), the Olvi Foundation (KK, no grant number), the Maire Taponen foundation (KK, no grant number), the Päivikki and Sakari Sohlberg Foundation (AH, no grant number), the Yrjö Jahnsson Foundation (AH, no grant number), the Finnish Cultural Foundation (KK, no grant number), the Maud Kuistila Memorial Foundation (KK, no grant number), the Finnish Brain Foundation (ES, no grant number; KK, no grant number; A-LH, grant no. 20190012), the Orion Research Foundation (ES, no grant number), the Instrumentarium Science Foundation (ES, no grant number), the Sigrid Jusélius Foundation (ES, AH, VL, no grant number), the Academy of Finland (AH, grant no 315459; AMR, grant no 315460; SH, PROFI5, grant no 325022; VL, grant no 339767), the KUH VTR Fund (VL, no grant number), and the ALS tutkimuksen tuki ry. registered association (NH, no grant number).
|Academy of Finland Grant Number:||
315460 (Academy of Finland Funding decision)
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