Neurofilament Light Chain as a Biomarker in Geriatric Psychiatry Practice: A Narrative Review

Neurofilament light chain (NFL) is a structural axonal protein released into extracellular fluids following neuroaxonal injury. Blood-based NfL measurement has emerged as a marker of neurodegeneration, but its relevance in geriatric psychiatry remains insufficiently defined. We conducted a narrative review of peer-reviewed studies reporting serum or plasma NfL concentrations in older adults with neurodegenerative diseases or major psychiatric disorders. In MEDLINE/PubMed, were searched up to 31 October 2025. We synthesised data on normative values and biological determinants, compared NfL levels across diagnostic categories, examined evidence from mild behavioral impairment and late-onset psychiatric presentations, and developed a clinically oriented interpretative framework. Across studies, blood NfL concentrations increased with age and were influenced by medical comorbidities, particularly renal function. Neurodegenerative disorders were associated with higher NfL levels than primary psychiatric disorders, whereas most psychiatric conditions overlapped with age-adjusted normative ranges. Meta-analytic evidence showed no significant elevation in major depressive disorder and modest, heterogeneous increases in bipolar disorder, while schizophrenia spectrum disorders largely overlapped with physiological ageing. In transdiagnostic contexts, including mild behavioral impairment and late-onset psychiatric syndromes, higher baseline NfL levels and steeper longitudinal increases were associated with greater risk of underlying neurodegeneration. These findings support a stepwise interpretation strategy integrating age, comorbidities, clinical context and longitudinal trajectories. Age- and comorbidity-adjusted interpretation of blood NfL can support risk stratification in geriatric psychiatry. Used as an adjunctive biomarker, NfL may help identify patients requiring monitoring or additional neurological assessment.