Blood-based biomarkers for neurodegenerative diseases: A narrative review

Blood-based biomarkers have revolutionized the diagnostic landscape for neurodegenerative diseases, offering accessible alternatives to invasive cerebrospinal fluid analysis and expensive neuroimaging. This narrative review synthesizes updated evidence on serum biomarkers across dementia, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, examining their utility for diagnosis, staging, differential diagnosis, and disease monitoring. Established markers, including amyloid-beta 42/40 ratio, glial fibrillary acidic protein, neurofilament light chain, and phosphorylated tau proteins, demonstrate validated clinical performance, while novel candidates spanning synaptic proteins, inflammatory mediators, and microRNAs offer enhanced mechanistic insights. Despite remarkable progress, significant translational challenges persist, including pre-analytical variability, lack of analytical standardization, uncertain cut-off values, and incomplete understanding of peripheral-to-central relationships. Addressing these barriers through international standardization initiatives, pragmatic clinical trials, and implementation guidelines will be essential to realize the promise of blood-based diagnostics. In summary, blood-based biomarkers hold immense transformative promise for enabling accessible and dynamic management of neurodegenerative diseases. Realizing this potential fully will require coordinated efforts to overcome current challenges in standardization and clinical validation.