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Serum total TDP-43 levels are decreased in frontotemporal dementia patients with C9orf72 repeat expansion or concomitant motoneuron disease phenotype |
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| Author: | Katisko, Kasper1; Huber, Nadine2; Kokkola, Tarja1; |
| Organizations: |
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 |
| Format: | article |
| Version: | published version |
| Access: | open |
| Online Access: | PDF Full Text (PDF, 1 MB) |
| Persistent link: | http://urn.fi/urn:nbn:fi-fe2023030129065 |
| Language: | English |
| Published: |
Springer Nature,
2022
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| Publish Date: | 2023-03-01 |
| Description: |
AbstractBackground: 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. see all
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| Series: |
Alzheimers research & therapy |
| ISSN: | 1758-9193 |
| ISSN-E: | 1758-9193 |
| ISSN-L: | 1758-9193 |
| Volume: | 14 |
| Issue: | 1 |
| Article number: | 151 |
| DOI: | 10.1186/s13195-022-01091-8 |
| OADOI: | https://oadoi.org/10.1186/s13195-022-01091-8 |
| Type of Publication: |
A1 Journal article – refereed |
| Field of Science: |
3124 Neurology and psychiatry |
| Subjects: | |
| Funding: |
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 |
| Detailed Information: |
315460 (Academy of Finland Funding decision) |
| Copyright information: |
© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
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https://creativecommons.org/licenses/by/4.0/ |