High-dimensional proteomic analysis for pathophysiological classification of traumatic brain injury

作者：Lucia M. Li, Eleftheria Kodosaki, Amanda Heslegrave, Henrik Zetterberg, Neil Graham, Karl Zimmerman, Eyal Soreq, Thomas D. Parker, Elena Garbero, Federico Moro, Sandra Magnoni, Guido Bertolini, David J. Loane, David Sharp · 发表于：Brain · 年份：2024 · DOI：10.1093/brain/awae305 · 被引用次数：25 · 研究领域：Traumatic Brain Injury and Neurovascular Disturbances、S100 Proteins and Annexins、Traumatic Brain Injury Research

Pathophysiology and outcomes after traumatic brain injury (TBI) are complex and heterogeneous. Current classifications are uninformative about pathophysiology. Proteomic approaches with fluid-based biomarkers are ideal for exploring complex disease mechanisms, because they enable sensitive assessment of an expansive range of processes potentially relevant to TBI pathophysiology. We used novel high-dimensional, multiplex proteomic assays to assess altered plasma protein expression in acute TBI. We analysed samples from 88 participants from the BIO-AX-TBI cohort [n = 38 moderate-severe TBI (Mayo Criteria), n = 22 non-TBI trauma and n = 28 non-injured controls] on two platforms: Alamar NULISA™ CNS Diseases and OLINK® Target 96 Inflammation. Patient participants were enrolled after hospital admission, and samples were taken at a single time point ≤10 days post-injury. Participants also had neurofilament light, GFAP, total tau, UCH-L1 (all Simoa®) and S100B (Millipore) data. The Alamar panel assesses 120 proteins, most of which were previously unexplored in TBI, plus proteins with known TBI specificity, such as GFAP. A subset (n = 29 TBI and n = 24 non-injured controls) also had subacute (10 days to 6 weeks post-injury) 3 T MRI measures of lesion volume and white matter injury (fractional anisotropy). Differential expression analysis identified 16 proteins with TBI-specific significantly different plasma expression. These were neuronal markers (calbindin 2, UCH-L1 and visinin-like...