Elevated Levels of Neurofilament Light and Heavy Chain as Diagnostic Biomarkers for ALS

Amyotrophic Lateral Sclerosis
Amyotrophic Lateral Sclerosis
Researchers analyzed cerebrospinal fluid and serum from patients with ALS to determine diagnostic biomarkers for the development of early treatment strategies.

Cerebrospinal fluid (CSF) neurofilament light (NfL), CSF neurofilament heavy (NfH), and serum NfL are effective biomarkers in the differential diagnosis of patients with amyotrophic lateral sclerosis (ALS), according to study findings published in Journal of Neurology, Neurosurgery and Psychiatry.

Compared with other neurodegenerative diseases, CSF and serum levels of NfL and NfH are elevated in patients with ALS. Moreover, neurofilaments in both the CSF and serum are elevated early in the disease, which may help in selecting treatment options for reducing ALS progression.

To evaluate the differential diagnostic potential of the CSF and serum neurofilament biomarkers for ALS, the current study authors sought to measure these biomarkers in patient groups, including those with ALS and other neurological diseases.

The CSF and serum specimens were collected from patients with ALS (n=75), with non-ALS but a previous differential diagnosis of ALS (n=60), frontotemporal lobar degeneration (FTLD; n=33), Alzheimer disease (AD; n=20), Parkinson disease (PD; n=18), Creutzfeldt-Jakob disease (CJD; n=11), and non-neurodegenerative disease control participants (n=77). The CJD samples were collected between 1997 and 2003 at the Department of Neurology in Göttingen, Germany, and all others were collected between 2014 and 2020 at the Department of Neurology in Ulm, Germany. Samples were assessed for differential features.

Patient groups were similar for all demographic features except for age, in which patients with PD were significantly older than those in the control (P =.003), non-ALS (P =.03), and ALS (P =.04) groups.

The NfL and NfH in the CSF and serum were significantly elevated in patients with ALS compared with control participants or non-ALS individuals (all P <.0001).

Compared with the other groups, the ALS group had significantly higher levels of CSF NfL compared with PD (P =.03); CSF NfH compared with those with FTLD (P =.0001) and those with AD (P =.004); serum NfL compared with those with AD (P <.0001) and those with FTLD (P =.04); and serum NfH compared with those with FTLD (P =.0008) and those with AD (P =.03).

Significant correlations were observed between all 6 biomarker combinations (all P <.0001); additional correlates included age (all P <.0001) and progression rates among patients with ALS (all P £.009).

The most effective cutoff rates for distinguishing between ALS and control and non-ALS groups were 1324 pg/mL and 1599 pg/mL for CSF NfL, 1598 pg/mL and 1754 pg/mL for CSF NfH, 45 pg/mL and 34 pg/mL for serum NfL, and 529 pg/mL and 627 pg/mL for serum NfH, respectively.

Study limitations included the reduced power for the serum NfH variable.

“To conclude, we here propose that for the diagnosis and differential diagnosis of ALS, CSF and serum NfL as well as CSF NfH are equally well-suited,” the researchers wrote.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Halbgebauer S, Steinacker P, Verde F, et al. Comparison of CSF and serum neurofilament light and heavy chain as differential diagnostic biomarkers for ALS. J Neurol Neurosurg Psychiatry. Published online August 20, 2021. doi:10.1136/jnnp-2021-327129