Advances in Circulating Biomarkers for Neurodegenerative Diseases, Traumatic Brain Injuries, and Central Nervous System Tumors
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Neurological disorders, including neurodegenerative diseases, traumatic brain injuries (TBI), and central nervous system (CNS) tumors, are complex conditions that significantly impact patients globally. Timely diagnosis and monitoring are critical for improving out- comes, driving the need for reliable biomarkers. Specifically, biomarkers detectable in ce- rebrospinal fluid (CSF) and blood offer important insights into disease presence and pro- gression. This review explores the evolution of circulating blood biomarkers for neurode- generative diseases, TBI, and CNS tumors, highlighting advanced detection technologies from enzyme-linked immunosorbent assays (ELISAs) to electrochemiluminescence (ECL) assays, single-molecule arrays (Simoa), and mass spectrometry. Advanced technologies with enhanced sensitivity and specificity, particularly in detecting low-abundance analytes, facilitate the investigation of CSF biomarkers for various neurological disorders. We also describe the progress in blood-based biomarkers for , emerging as less invasive alterna- tives to CSF sampling. Clinically, the implementation of Alzheimer’s disease (AD) blood bio- Received: November 12, 2024 Revision received: January 9, 2025 Accepted: June 10, 2025 Published online: June 18, 2025 Corresponding author: Jing Cao, Ph.D. Department of Pathology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA E-mail: Jing.Cao2@UTSouthwestern.edu markers Aβ /Aβ 42 40 ratio and Apolipoprotein E isoform-specific peptide can aid the diagno- sis, while p-tau181 and p-tau217 differentiates AD dementia from non-AD neurodegenera- tive diseases. Blood glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 are used in ruling out mild TBI. Despite these innovations, challenges remain, including assay standardization, sensitivity/specificity trade-offs, and the requirement for longitudinal studies to understand biomarker utility over time. Future research should focus on ad- dressing these challenges to fully realize the potential of blood-based biomarkers in neuro- logical disorder diagnostics and patient care.
Abstract
Neurological disorders, including neurodegenerative diseases, traumatic brain injuries (TBI), and central nervous system (CNS) tumors, are complex conditions that significantly impact patients globally. Timely diagnosis and monitoring are critical for improving out- comes, driving the need for reliable biomarkers. Specifically, biomarkers detectable in ce- rebrospinal fluid (CSF) and blood offer important insights into disease presence and pro- gression. This review explores the evolution of circulating blood biomarkers for neurode- generative diseases, TBI, and CNS tumors, highlighting advanced detection technologies from enzyme-linked immunosorbent assays (ELISAs) to electrochemiluminescence (ECL) assays, single-molecule arrays (Simoa), and mass spectrometry. Advanced technologies with enhanced sensitivity and specificity, particularly in detecting low-abundance analytes, facilitate the investigation of CSF biomarkers for various neurological disorders. We also describe the progress in blood-based biomarkers for , emerging as less invasive alterna- tives to CSF sampling. Clinically, the implementation of Alzheimer’s disease (AD) blood bio- Received: November 12, 2024 Revision received: January 9, 2025 Accepted: June 10, 2025 Published online: June 18, 2025 Corresponding author: Jing Cao, Ph.D. Department of Pathology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA E-mail: Jing.Cao2@UTSouthwestern.edu markers Aβ /Aβ 42 40 ratio and Apolipoprotein E isoform-specific peptide can aid the diagno- sis, while p-tau181 and p-tau217 differentiates AD dementia from non-AD neurodegenera- tive diseases. Blood glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 are used in ruling out mild TBI. Despite these innovations, challenges remain, including assay standardization, sensitivity/specificity trade-offs, and the requirement for longitudinal studies to understand biomarker utility over time. Future research should focus on ad- dressing these challenges to fully realize the potential of blood-based biomarkers in neuro- logical disorder diagnostics and patient care.