To assess the utility of plasma neurofilament light chain (pNfL) as a biomarker of neurodegenerative diseases using a fixed threshold for screening in clinical practice.

Elevated pNfL is a marker of neuroaxonal injury in neurodegenerative diseases. However, no threshold has been established for clinically meaningful pNfL elevations for use as a routine screening tool in primary care settings. 

For this post hoc analysis, baseline pNfL levels were analyzed from Phase III studies of patients with Stage I or II Huntington’s disease (HD; NCT03664804; n=89), prodromal to mild Alzheimer’s disease (AD; NCT03114657; n=1124), early Parkinson’s disease (PD; NCT03100149; n=270) and a cohort of healthy controls (HC; n=690) using the Elecsys platform, and among patients with primary progressive multiple sclerosis (PPMS; NCT01194570; n=498) and an HC cohort (n=117) using the Quanterix pNfL Advantage kit. Median ± IQR unadjusted pNfL levels were calculated, and differences from median HC levels were determined for disease cohorts.

In patients with HD, pNfL levels were elevated 12.9-fold over the HC median level. pNfL levels were elevated to a lesser extent in patients with AD (1.5-fold) and were slightly lower than HCs among patients with early PD (0.9-fold). Among patients with PPMS, pNfL levels were elevated 1.8-fold over the HC median. For all disease cohorts except HD, pNfL IQRs overlapped with those of HCs.

Elevated pNfL levels vs HCs were observed among HD, AD, and PPMS cohorts but not in early PD, consistent with previous reports. However, no clinically meaningful threshold using a fixed cutoff for pNfL elevation across neurodegenerative diseases could be established. The findings from this study, the first to evaluate pNfL levels from clinical trials across multiple neurological diseases, support further investigation of the clinical utility of pNfL as a neurological screen in primary care.