For ALS Diagnosis, Study Shows Serum NfL Was More Accurate than p-tau181 or GFAP

Serum neurofilament light chain (NfL) levels demonstrated greater diagnostic and prognostic accuracy as a biomarker for amyotrophic lateral sclerosis (ALS) than glial fibrillary acidic protein (GFAP) or phosphorylated tau 181 (p-tau181), according to findings published in Neurology. The study, supported by the French Foundation for Medical Research (FRM; Paris, France) and AXA (Paris, France) included 4 separate immunoassay methods in its analysis, each of which demonstrated high and consistent clinical performance: Simoa HD-X (Quanterix, Billerica, MA), Ella (Bio-Techne, Minnneapolis, MN), Lumipulse G1200 (Fujirebio, Malvern, PA), and Elecsys (Roche, Indianapolis, IN).

The total population of this multicenter study comprised 209 adult participants, including 139 with an ALS diagnosis and 70 with a non-ALS neuromuscular disorder. Serum samples were collected from all participants and assessed for GFAP, p-tau181, and NfL levels as measured by 4 immunoassays.

For participants with ALS, the mean follow-up was 42 ±26.3 months with an 85.5% mortality rate. For those without ALS, there was a mean follow-up of 141.6 ±106.3 months and a 7.7% mortality rate. The area under the curve (AUC) values of serum biomarker tests for ALS diagnosis were as follows:

• NfL:
  • Simoa HD-X: .889 (95% CI, .827 to .932)
  • Ella: .906 (95% CI, .847 to .944)
  • Lumipulse: .912 (95% CI, .853 to .948)
  • Elecsys: .910 (95% CI, .851 to .946)
• p-tau181: .565 (95% CI, .472 to .649)
• GFAP: .546 (95% CI, .461 to .636)

Results demonstrated that >80% of people with ALS were identified using serum NfL (P<.0001)—significantly more accurate than the p-tau181 and GFAP tests. Additionally, researchers identified hazard ratios of 4.4 to 5.4 for serum NfL. Individuals with ALS below this prognostic cutoff had a 40% to 50% chance of surviving for 50 weeks, while those above had a survival rate near 0%.