INTRODUCTIONMany patients with neurodegenerative disorders (ND) face diagnostic delay and misdiagnosis. We investigated blood and cerebrospinal fluid (CSF) neurofilament light chain (NfL) to distinguish ND from primary psychiatric disorders (ND), a common challenge in clinical settings.METHODSPlasma and CSF NfL levels were measured and compared between groups, adjusting for age, sex, weight.RESULTS337 participants included: 136 ND, 77 PPD, 124 Controls. Plasma NfL was 2.5 fold elevated in ND compared to PPD and had strong diagnostic performance (area under the curve, AUC 0.86, 81%/85% specificity/sensitivity) that was comparable to CSF NfL (2 fold elevated, AUC 0.89, 95%/71% specificity/sensitivity). Diagnostic performance was especially strong in younger people (40-<60years). Additional findings were cut-offs optimised for sensitivity and specificity, and issues important for future clinical translationCONCLUSIONSThis study adds important evidence for a simple blood-based biomarker to assist as a screening test for neurodegeneration and distinction from PPD, in clinical settings.