Plasma Biomarkers and Positron Emission Tomography Tau Pathology in Progressive Supranuclear Palsy

ABSTRACT Background Development of disease‐modifying therapeutic trials of progressive supranuclear palsy (PSP) urges the need for sensitive fluid biomarkers. Objectives The objectives of this study were to explore the utility of plasma biomarkers in the diagnosis, differential diagnosis, and assessment of disease severity, brain atrophy, and tau deposition in PSP. Methods Plasma biomarkers were measured using a single‐molecule array in a cohort composed of patients with PSP, Parkinson's disease (PD), multiple system atrophy with predominant parkinsonism (MSA‐P), and healthy controls (HCs). Results Plasma neurofilament light chain (NfL) outperformed other plasma makers (ie, glial fibrillary acidic protein [GFAP], phosphorylated‐tau 181 [p‐tau181], amyloid‐β 1–40, amyloid‐β 1–42) in identifying PSP from HC (area under the curve [AUC] = 0.904) and from MSA‐P (AUC = 0.711). Plasma GFAP aided in distinguishing PSP from HC (AUC = 0.774) and from MSA‐P (AUC = 0.832). It correlated with brainstem atrophy and higher regional tau accumulation. However, plasma p‐tau181 neither helped in diagnosis nor was it associated with clinical or neuroimaging measures. Conclusions Plasma NfL and GFAP showed different values in differentiating PSP from HC or controls with other forms of neurodegenerative parkinsonism and detecting disease severity, brain atrophy, or tau deposition in PSP. © 2023 International Parkinson and Movement Disorder Society.