Plasma and CSF neurofilament light chain distinguish neurodegenerative from primary psychiatric conditions in a clinical setting

Abstract

ABSTRACTINTRODUCTIONMany 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.