From Brain to Blood: Point-of-Care Detection of Biomarkers in Neurological Diseases.

Neurological diseases (NDs) continue to be a leading cause of disability and mortality worldwide, largely due to delayed diagnosis and limited access to rapid assessment. Blood-based biomarkers (BBMs) provide minimally invasive, objective, and early molecular indicators of pathological changes in the brain. By combining sensitive signal transduction, simplified sample processing, and rapid readout, point-of-care testing (POCT) technologies offer transformative opportunities to translate BBM discoveries into real-time and decentralized neurological diagnostics. This review systematically categorizes the most widely studied and translationally valuable neurological BBMs and discusses their biological features and clinical relevance, with emphasis on their kinetics, diagnostic specificity, and analytical requirements. We further discuss emerging sensing strategies enabling sensitive and rapid BBM detection, focusing on signal amplification performance, multiplex detection capabilities, and readout time of electrochemical biosensors and optical biosensors, as well as their combination with paper-based devices, microfluidics, smartphones, and artificial intelligence. Importantly, we discuss the rational matching of different sensing modalities with the physicochemical characteristics of specific biomarkers. Moreover, we examine clinical needs and commercially available POCT strategies for NDs, highlighting two disease-oriented scenarios: rapid diagnosis for acute neurological injuries and self-screening and longitudinal monitoring for chronic neurodegenerative disorders. Finally, we provide a dedicated section on the key translation challenges facing neurological BBM-based POCT devices. Together, by integrating biomarker biology, advanced sensing technologies, and disease-specific clinical needs, this review proposes a biomarker- and disease-oriented framework for neurological POCT development. This framework aims to accelerate the development of clinically actionable diagnostic tools that support timely screening, early diagnosis, risk stratification, and longitudinal monitoring across the continuum of neurological care.