Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis

Abstract

ObjectiveTo determine the diagnostic and prognostic performance of serum neurofilament light chain (NFL) in amyotrophic lateral sclerosis (ALS).MethodsThis single-centre, prospective, longitudinal study included the following patients: 124 patients with ALS; 50 patients without neurodegenerative diseases; 44 patients with conditions included in the differential diagnosis of ALS (disease controls); 65 patients with other neurodegenerative diseases (20 with frontotemporal dementia, 20 with Alzheimer’s disease, 19 with Parkinson’s disease, 6 with Creutzfeldt-Jakob disease (CJD)). Serum NFL levels were measured using the ultrasensitive single molecule array (Simoa) technology.ResultsSerum NFL levels were higher in ALS in comparison to all other categories except for CJD. A cut-off level of 62 pg/mL discriminated between ALS and all other conditions with 85.5% sensitivity (95% CI 78% to 91.2%) and 81.8% specificity (95% CI 74.9% to 87.4%). Among patients with ALS, serum NFL correlated positively with disease progression rate (rs=0.336, 95% CI 0.14 to 0.506, p=0.0008), and higher levels were associated with shorter survival (p=0.0054). Serum NFL did not differ among patients in different ALS pathological stages as evaluated by diffusion-tensor imaging, and in single patients NFL levels were stable over time.ConclusionsSerum NFL is increased in ALS in comparison to other conditions and can serve as diagnostic and prognostic biomarker. We established a cut-off level for the diagnosis of ALS.

The diagnostic performance of neurofilament light chain in CSF and blood for Alzheimer's disease, frontotemporal dementia, and amyotrophic lateral sclerosis: A systematic review and meta‐analysis

“…4C). Ten of these studies compared serum NfL concentration (693 ALS cases and 413 cognitively unimpaired controls) [4,51,64–67,74,76], with an average mean ratio of 9.80 (95% CI 5.14–18.69). A single study also investigated plasma NfL concentration in 103 ALS cases and 42 cognitively unimpaired controls [66], with a ratio of 3.58 (95% CI 2.83–4.52).…”

“…Twelve studies compared blood (i.e., plasma and serum) NfL concentration in AD cases and cognitively unimpaired controls [4,9,25,30,42,[47][48][49][50][51][52][53]; however, three of these studies used largely overlapping data from the ADNI database [49,50,53]. To avoid bias, the largest of the three overlapping studies was selected for inclusion in the meta-analysis [53]; thus, 10 studies comparing 471 AD cases to 518 cognitively unimpaired controls were included in the meta-analysis.…”

“…Of these studies, 5 studies (365 AD cases and 357 cognitively unimpaired controls) compared NfL concentration in plasma, with an average ratio of 2.11 (95% CI 0.78-5.73) [25,30,47,48,53]. The remaining 5 studies (106 AD cases and 161 cognitively unimpaired controls) compared serum NfL concentration [4,9,42,51,52], with an average ratio of 3.22 (95% CI 1.37-7.57). A between-subgroup comparison indicated that the NfL concentration ratio for AD to cognitively unimpaired controls was statistically indistinguishable in serum and plasma (Q (1) 5 0.80, P 5 0.371).…”

“…Five studies investigated blood NfL concentration in FTD cases compared with controls [4,9,51,59,63]. Four of these studies compared serum NfL concentration in 202 FTD cases and 139 cognitively unimpaired controls, with an average mean ratio of 2.65 (95% CI 1.59-4.43, P 5 0.009; Fig.…”

“…Eleven studies compared blood NfL concentration from ALS cases (n 5 796) and cognitively unimpaired controls (n 5 455) [4,51,59,[64][65][66][67]71,74,76], with an average ratio of 8.92 (95% CI 4.85-16.43, P , 0.0001; Fig. 4C).…”