Serum glial fibrillary acid protein associates with TSPO-expressing lesions in multiple sclerosis brain

Tanja Sjöros; Maija Saraste; Markus Matilainen; Marjo Nylund; Mikko Koivumäki; Jens Kuhle; David Leppert; Laura Airas

doi:10.1177/17562864251352998

Serum glial fibrillary acid protein associates with TSPO-expressing lesions in multiple sclerosis brain

Tanja Sjöros^*
, Maija Saraste
, Markus Matilainen
, Marjo Nylund
, Mikko Koivumäki
, Jens Kuhle
, David Leppert
, Laura Airas

^*Corresponding author for this work

Research output: Contribution to journal › Article › Scientific › peer-review

Abstract

Background: Serum glial fibrillary acidic protein (sGFAP) is a promising biomarker for multiple sclerosis (MS) disease progression. Elevated sGFAP levels are considered to reflect ongoing astrocyte-related pathology in the central nervous system. Objectives: To study whether sGFAP levels associate with 18 kDa translocator protein (TSPO) availability in MS brain. TSPO is a mitochondrial molecule that is expressed by activated microglia and astrocytes. Design: Cross-sectional multimodal biomarker correlation study. Methods: We included 80 people with MS (66 relapsing-remitting and 14 progressive MS, 69% women), and 11 healthy control participants (73% women). sGFAP was measured using single molecule array (Simoa®) technology in combination with 3T magnetic resonance imaging and positron emission tomography (PET) using a TSPO-binding [¹¹C]PK11195 radioligand. Results: sGFAP was higher among people with progressive MS (median 122 pg/ml) compared to healthy controls (median 59 pg/ml, p = 0.0002) or participants with relapsing-remitting MS (median 77 pg/ml, p = 0.0056). Among people with MS, higher sGFAP associated with higher volume of chronic lesions with increased TSPO activity (r = 0.36, p = 0.0011) and with thalamic TSPO activity (r = 0.30, p = 0.0069), as well as with T1 and T2 lesion loads (r = 0.38, 0.41, p = 0.0005, 0.0002, respectively). Smaller normal-appearing white matter (r = −0.36, p = 0.0009), cortical gray matter, and thalamus volumes (r = −0.39, p = 0.0003 for both) correlated with higher sGFAP. In regression analyses, the volume of TSPO-expressing lesions, together with age and MS disease-modifying treatment status, explained 27% of the variation in sGFAP. Conclusion: sGFAP associates with adverse magnetic resonance imaging and PET imaging outcomes. The association between a high prevalence of TSPO-expressing white matter lesions and high sGFAP suggests that lesion-associated glial activity promotes MS progression partially via astrocyte-driven mechanisms. A combination of various soluble biomarkers and PET ligands for specific cell types may add to the understanding of progression-promoting cellular mechanisms in the brain. Trial registration: ClinicalTrials.gov NCT03134716, NCT03368677, NCT04126772, NCT04239820, https://clinicaltrials.gov.

Original language	English
Article number	17562864251352998
Journal	Therapeutic advances in neurological disorders
Volume	18
DOIs	https://doi.org/10.1177/17562864251352998
Publication status	Published - Nov 2025
MoE publication type	A1 Journal article-refereed

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was financially supported by the Research Council of Finland grant for clinical researcher (decision number 330902), the Research Council of Finland’s Flagship InFLAMES (decision numbers 337530, 357910 and 358823), The Jane and Aatos Erkko foundation (#220026), a Grant from the National MS Society and the National Stem Cell Foundation (RFA-2203-39281), and the State Research Funding (SRF) for university-level health research, Turku University Hospital, Wellbeing Services County of Southwest Finland. This study was conducted within the Turku PET Centre, supported by the University of Turku, Turku University Hospital, and Åbo Akademi University. We thank the staff in the Turku PET Centre for their proficient assistance in conducting the study, Eveliina Honkonen, Marcus Sucksdorff, Jussi Lehto, Anna Vuorimaa, and Sini Laaksonen for data acquisition, and Eliisa Löyttyniemi for guidance on the statistical methods. This study was conducted within the Turku PET Centre, supported by the University of Turku, Turku University Hospital, and Åbo Akademi University. We thank the staff in the Turku PET Centre for their proficient assistance in conducting the study, Eveliina Honkonen, Marcus Sucksdorff, Jussi Lehto, Anna Vuorimaa, and Sini Laaksonen for data acquisition, and Eliisa Löyttyniemi for guidance on the statistical methods. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was financially supported by the Research Council of Finland grant for clinical researcher (decision number 330902), the Research Council of Finland’s Flagship InFLAMES (decision numbers 337530, 357910 and 358823), The Jane and Aatos Erkko foundation (#220026), a Grant from the National MS Society and the National Stem Cell Foundation (RFA-2203-39281), and the State Research Funding (SRF) for university-level health research, Turku University Hospital, Wellbeing Services County of Southwest Finland.

Keywords

18 kDa translocator protein
astrocyte
brain imaging
glial fibrillary acid protein
magnetic resonance imaging
microglia
multiple sclerosis
neuroinflammation
positron emission tomography

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10.1177/17562864251352998Licence: CC BY

sjöros-et-al-2025-serum-glial-fibrillary-acid-protein-associates-with-tspo-expressing-lesions-in-multiple-sclerosisFinal published version, 754 KBLicence: CC BY

https://urn.fi/URN:NBN:fi-fe2026022716735

Cite this

@article{0c739ffdbdf9424080680b66b05182df,

title = "Serum glial fibrillary acid protein associates with TSPO-expressing lesions in multiple sclerosis brain",

abstract = "Background: Serum glial fibrillary acidic protein (sGFAP) is a promising biomarker for multiple sclerosis (MS) disease progression. Elevated sGFAP levels are considered to reflect ongoing astrocyte-related pathology in the central nervous system. Objectives: To study whether sGFAP levels associate with 18 kDa translocator protein (TSPO) availability in MS brain. TSPO is a mitochondrial molecule that is expressed by activated microglia and astrocytes. Design: Cross-sectional multimodal biomarker correlation study. Methods: We included 80 people with MS (66 relapsing-remitting and 14 progressive MS, 69\% women), and 11 healthy control participants (73\% women). sGFAP was measured using single molecule array (Simoa{\textregistered}) technology in combination with 3T magnetic resonance imaging and positron emission tomography (PET) using a TSPO-binding [11C]PK11195 radioligand. Results: sGFAP was higher among people with progressive MS (median 122 pg/ml) compared to healthy controls (median 59 pg/ml, p = 0.0002) or participants with relapsing-remitting MS (median 77 pg/ml, p = 0.0056). Among people with MS, higher sGFAP associated with higher volume of chronic lesions with increased TSPO activity (r = 0.36, p = 0.0011) and with thalamic TSPO activity (r = 0.30, p = 0.0069), as well as with T1 and T2 lesion loads (r = 0.38, 0.41, p = 0.0005, 0.0002, respectively). Smaller normal-appearing white matter (r = −0.36, p = 0.0009), cortical gray matter, and thalamus volumes (r = −0.39, p = 0.0003 for both) correlated with higher sGFAP. In regression analyses, the volume of TSPO-expressing lesions, together with age and MS disease-modifying treatment status, explained 27\% of the variation in sGFAP. Conclusion: sGFAP associates with adverse magnetic resonance imaging and PET imaging outcomes. The association between a high prevalence of TSPO-expressing white matter lesions and high sGFAP suggests that lesion-associated glial activity promotes MS progression partially via astrocyte-driven mechanisms. A combination of various soluble biomarkers and PET ligands for specific cell types may add to the understanding of progression-promoting cellular mechanisms in the brain. Trial registration: ClinicalTrials.gov NCT03134716, NCT03368677, NCT04126772, NCT04239820, https://clinicaltrials.gov.",

keywords = "18 kDa translocator protein, astrocyte, brain imaging, glial fibrillary acid protein, magnetic resonance imaging, microglia, multiple sclerosis, neuroinflammation, positron emission tomography",

author = "Tanja Sj{\"o}ros and Maija Saraste and Markus Matilainen and Marjo Nylund and Mikko Koivum{\"a}ki and Jens Kuhle and David Leppert and Laura Airas",

note = "Publisher Copyright: {\textcopyright} The Author(s), 2025. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).",

year = "2025",

month = nov,

doi = "10.1177/17562864251352998",

language = "English",

volume = "18",

journal = "Therapeutic advances in neurological disorders",

issn = "1756-2856",

publisher = "Sage publications",

}

TY - JOUR

T1 - Serum glial fibrillary acid protein associates with TSPO-expressing lesions in multiple sclerosis brain

AU - Sjöros, Tanja

AU - Saraste, Maija

AU - Matilainen, Markus

AU - Nylund, Marjo

AU - Koivumäki, Mikko

AU - Kuhle, Jens

AU - Leppert, David

AU - Airas, Laura

N1 - Publisher Copyright: © The Author(s), 2025. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

PY - 2025/11

Y1 - 2025/11

N2 - Background: Serum glial fibrillary acidic protein (sGFAP) is a promising biomarker for multiple sclerosis (MS) disease progression. Elevated sGFAP levels are considered to reflect ongoing astrocyte-related pathology in the central nervous system. Objectives: To study whether sGFAP levels associate with 18 kDa translocator protein (TSPO) availability in MS brain. TSPO is a mitochondrial molecule that is expressed by activated microglia and astrocytes. Design: Cross-sectional multimodal biomarker correlation study. Methods: We included 80 people with MS (66 relapsing-remitting and 14 progressive MS, 69% women), and 11 healthy control participants (73% women). sGFAP was measured using single molecule array (Simoa®) technology in combination with 3T magnetic resonance imaging and positron emission tomography (PET) using a TSPO-binding [11C]PK11195 radioligand. Results: sGFAP was higher among people with progressive MS (median 122 pg/ml) compared to healthy controls (median 59 pg/ml, p = 0.0002) or participants with relapsing-remitting MS (median 77 pg/ml, p = 0.0056). Among people with MS, higher sGFAP associated with higher volume of chronic lesions with increased TSPO activity (r = 0.36, p = 0.0011) and with thalamic TSPO activity (r = 0.30, p = 0.0069), as well as with T1 and T2 lesion loads (r = 0.38, 0.41, p = 0.0005, 0.0002, respectively). Smaller normal-appearing white matter (r = −0.36, p = 0.0009), cortical gray matter, and thalamus volumes (r = −0.39, p = 0.0003 for both) correlated with higher sGFAP. In regression analyses, the volume of TSPO-expressing lesions, together with age and MS disease-modifying treatment status, explained 27% of the variation in sGFAP. Conclusion: sGFAP associates with adverse magnetic resonance imaging and PET imaging outcomes. The association between a high prevalence of TSPO-expressing white matter lesions and high sGFAP suggests that lesion-associated glial activity promotes MS progression partially via astrocyte-driven mechanisms. A combination of various soluble biomarkers and PET ligands for specific cell types may add to the understanding of progression-promoting cellular mechanisms in the brain. Trial registration: ClinicalTrials.gov NCT03134716, NCT03368677, NCT04126772, NCT04239820, https://clinicaltrials.gov.

AB - Background: Serum glial fibrillary acidic protein (sGFAP) is a promising biomarker for multiple sclerosis (MS) disease progression. Elevated sGFAP levels are considered to reflect ongoing astrocyte-related pathology in the central nervous system. Objectives: To study whether sGFAP levels associate with 18 kDa translocator protein (TSPO) availability in MS brain. TSPO is a mitochondrial molecule that is expressed by activated microglia and astrocytes. Design: Cross-sectional multimodal biomarker correlation study. Methods: We included 80 people with MS (66 relapsing-remitting and 14 progressive MS, 69% women), and 11 healthy control participants (73% women). sGFAP was measured using single molecule array (Simoa®) technology in combination with 3T magnetic resonance imaging and positron emission tomography (PET) using a TSPO-binding [11C]PK11195 radioligand. Results: sGFAP was higher among people with progressive MS (median 122 pg/ml) compared to healthy controls (median 59 pg/ml, p = 0.0002) or participants with relapsing-remitting MS (median 77 pg/ml, p = 0.0056). Among people with MS, higher sGFAP associated with higher volume of chronic lesions with increased TSPO activity (r = 0.36, p = 0.0011) and with thalamic TSPO activity (r = 0.30, p = 0.0069), as well as with T1 and T2 lesion loads (r = 0.38, 0.41, p = 0.0005, 0.0002, respectively). Smaller normal-appearing white matter (r = −0.36, p = 0.0009), cortical gray matter, and thalamus volumes (r = −0.39, p = 0.0003 for both) correlated with higher sGFAP. In regression analyses, the volume of TSPO-expressing lesions, together with age and MS disease-modifying treatment status, explained 27% of the variation in sGFAP. Conclusion: sGFAP associates with adverse magnetic resonance imaging and PET imaging outcomes. The association between a high prevalence of TSPO-expressing white matter lesions and high sGFAP suggests that lesion-associated glial activity promotes MS progression partially via astrocyte-driven mechanisms. A combination of various soluble biomarkers and PET ligands for specific cell types may add to the understanding of progression-promoting cellular mechanisms in the brain. Trial registration: ClinicalTrials.gov NCT03134716, NCT03368677, NCT04126772, NCT04239820, https://clinicaltrials.gov.

KW - 18 kDa translocator protein

KW - astrocyte

KW - brain imaging

KW - glial fibrillary acid protein

KW - magnetic resonance imaging

KW - microglia

KW - multiple sclerosis

KW - neuroinflammation

KW - positron emission tomography

UR - https://www.scopus.com/pages/publications/105013129025

U2 - 10.1177/17562864251352998

DO - 10.1177/17562864251352998

M3 - Article

AN - SCOPUS:105013129025

SN - 1756-2856

VL - 18

JO - Therapeutic advances in neurological disorders

JF - Therapeutic advances in neurological disorders

M1 - 17562864251352998

ER -

Serum glial fibrillary acid protein associates with TSPO-expressing lesions in multiple sclerosis brain

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