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

• Published in: Therapeutic advances in neurological disorders Vol. 18; p. 17562864251352998
• Main Authors: Sjöros, Tanja, Saraste, Maija, Matilainen, Markus, Nylund, Marjo, Koivumäki, Mikko, Kuhle, Jens, Leppert, David, Airas, Laura
• Format: Journal Article
• Language: English
• Published: England SAGE Publishing 01.01.2025
• Subjects: brain imaging; magnetic resonance imaging; neuroinflammation; multiple sclerosis; 18 kDa translocator protein; glial fibrillary acid protein; positron emission tomography; astrocyte; microglia
• ISSN: 1756-2864; 1756-2856; 1756-2864
• DOI: 10.1177/17562864251352998

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. 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. Cross-sectional multimodal biomarker correlation study. 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 [ C]PK11195 radioligand. sGFAP was higher among people with progressive MS (median 122 pg/ml) compared to healthy controls (median 59 pg/ml,  = 0.0002) or participants with relapsing-remitting MS (median 77 pg/ml,  = 0.0056). Among people with MS, higher sGFAP associated with higher volume of chronic lesions with increased TSPO activity (  = 0.36,  = 0.0011) and with thalamic TSPO activity (  = 0.30,  = 0.0069), as well as with T1 and T2 lesion loads (  = 0.38, 0.41,  = 0.0005, 0.0002, respectively). Smaller normal-appearing white matter (  = -0.36,  = 0.0009), cortical gray matter, and thalamus volumes (  = -0.39,  = 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. 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. ClinicalTrials.gov NCT03134716, NCT03368677, NCT04126772, NCT04239820, https://clinicaltrials.gov.