Evaluation of Blood Glial Fibrillary Acidic Protein as a Potential Marker in Huntington's Disease

Abstract

Objective: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. Neurofilament light protein (NfL) is correlated with clinical severity of HD but relative data are the lack in the Chinese population. Reactive astrocytes are related to HD pathology, which predicts their potential to be a biomarker in HD progression. Our aim was to discuss the role of blood glial fibrillary acidic protein (GFAP) to evaluate clinical severity in patients with HD.Methods: Fifty-seven HD mutation carriers (15 premanifest HD, preHD, and 42 manifest HD) and 26 healthy controls were recruited. Demographic data and clinical severity assessed with the internationally Unified Huntington's Disease Rating Scale (UHDRS) were retrospectively analyzed. Plasma NfL and GFAP were quantified with an ultra-sensitive single-molecule (Simoa, Norcross, GA, USA) technology. We explored their consistency and their correlation with clinical severity.Results: Compared with healthy controls, plasma NfL (p < 0.0001) and GFAP (p < 0.001) were increased in Chinese HD mutation carriers, and they were linearly correlated with each other (r = 0.612, p < 0.001). They were also significantly correlated with disease burden, Total Motor Score (TMS) and Total Functional Capacity (TFC). The scores of Stroop word reading, symbol digit modalities tests, and short version of the Problem Behaviors Assessments (PBAs) for HD were correlated with plasma NfL but not GFAP. Compared with healthy controls, plasma NfL has been increased since stage 1 but plasma GFAP began to increase statistically in stage 2.Conclusions: Plasma GFAP was correlated with plasma NfL, disease burden, TMS, and TFC in HD mutation carriers. Plasma GFAP may have potential to be a sensitive biomarker for evaluating HD progression.

Investigating the Gliogenic Genes and Signaling Pathways in the Pathogenesis of Huntington’s Disease: A Systematic Review

“…Glial Fibrillary Acidic Protein (GFAP) and S100 proteins are both key markers of glial cells and play important roles in gliogenesis, the process of generating glial cells from neural progenitor cells [71].…”

“…Its expression is a hallmark of mature astrocytes, and it contributes to the structural integrity of these cells [72]. S100 proteins are a family of calcium-binding proteins that are predominantly found in glial cells, including astrocytes [73]. They play roles in cell cycle regulation, calcium homeostasis, and other intracellular processes.…”

Sex differences in Huntington's disease from a neuroinflammation perspective

“…Upregulation of the intermediate filament glial fibrillary acidic protein (GFAP) is essential for the transition of astrocytes to a reactive state ( 46 ). A recent study identified a significant elevation in plasma GFAP concentration in HD patients with the HTT mutation, suggesting its association with HD progression ( 47 ). Female mice were found to have significantly higher GFAP signals than males ( 48 , 49 ), indicating that female astrocytes may be more prone to inflammation than males in the context of HD.…”