Brain-Derived Neurotrophic Factor in Neurodegenerative Diseases: Biomarker Evidence and Therapeutic Perspectives

Brain-derived neurotrophic factor (BDNF) is a key regulator of neuronal survival, synaptic plasticity, and neurogenesis and has emerged as a potential biomarker and therapeutic target in neurodegenerative diseases. This narrative review critically summarizes current evidence on BDNF dysregulation in Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis, with emphasis on biomarker potential, therapeutic modulation, and translational challenges. Relevant literature was identified through targeted PubMed searches and reference-list screening, prioritizing original experimental and clinical studies, meta-analyses, and recent reviews. Altered BDNF expression and impaired signaling through tropomyosin receptor kinase B (TrkB) and the p75 neurotrophin receptor (p75NTR) are implicated in synaptic dysfunction, disrupted axonal transport, abnormal protein-related pathology, and neuronal vulnerability. Peripheral and central BDNF alterations have been associated with disease severity, but methodological heterogeneity and inconsistent findings for variants such as Val66Met limit biomarker application. TrkB-targeting approaches, gene delivery, pharmacological modulation of BDNF-related pathways, and physical activity show neuroprotective potential, predominantly in experimental studies. BDNF therefore represents a promising translational link between neurodegenerative mechanisms, biomarker development, and therapeutic innovation, but clinical translation requires standardized assessment, improved delivery strategies, biomarker-guided patient selection, and selective modulation of disease- and receptor-specific signaling.