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

Abstract

<h3>Background:</h3><p>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.</p><h3>Objectives:</h3><p>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.</p><h3>Design:</h3><p>Cross-sectional multimodal biomarker correlation study.</p><h3>Methods:</h3><p>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.</p><h3>Results:</h3><p>sGFAP was higher among people with progressive MS (median 122 pg/ml) compared to healthy controls (median 59 pg/ml, <em>p</em> = 0.0002) or participants with relapsing-remitting MS (median 77 pg/ml, <em>p</em> = 0.0056). Among people with MS, higher sGFAP associated with higher volume of chronic lesions with increased TSPO activity (<em>r</em> = 0.36, <em>p</em> = 0.0011) and with thalamic TSPO activity (<em>r</em> = 0.30, <em>p</em> = 0.0069), as well as with T1 and T2 lesion loads (<em>r</em> = 0.38, 0.41, <em>p</em> = 0.0005, 0.0002, respectively). Smaller normal-appearing white matter (<em>r</em> = −0.36, <em>p</em> = 0.0009), cortical gray matter, and thalamus volumes (<em>r</em> = −0.39, <em>p</em> = 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.</p><h3>Conclusion:</h3><p>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.</p>