Perry Daniel¹, Young Ethan², Perry Ella³, Lewis Noah⁴, Bennett Ella⁵, Harris Mia⁶, Thompson Sophia⁷
ABSTRACT:
Neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), are characterized by progressive neuronal loss and protein aggregation, yet early diagnosis and monitoring remain challenging. This review evaluates the clinical utility of neurofilament light chain (NfL) and tau protein as quantifiable fluid biomarkers in cerebrospinal fluid (CSF) and blood. NfL, a marker of neuroaxonal injury, correlates with disease progression across multiple neurodegenerative conditions, while tau species (e.g., p-tau181, p-tau217) reflect tauopathy burden in AD. We discuss advances in ultrasensitive immunoassays, their role in differential diagnosis, and the potential to guide therapeutic trials. Challenges in standardization, preanalytical variability, and the integration of multi-modal biomarkers (e.g., amyloid-β, α-synuclein) are addressed. The review concludes with future directions, including the synergy of fluid biomarkers with neuroimaging and digital phenotyping for precision neurology.