Elevated concentrations of Neurofilament Light and Heavy Chain as diagnostic biomarkers for ALS

According to study results published in the Journal of Neurology, Neurosurgery and Psychiatrie.

Compared to other neurodegenerative diseases, the CSF and serum levels of NfL and NfH are increased in patients with ALS. In addition, neurofilaments in both CSF and serum are increased at the onset of the disease, which can help in choosing treatment options to reduce ALS progression.

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

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The CSF and serum samples were obtained 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’s disease (AD; n = 20), Parkinson’s 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 Neurology in Göttingen, Germany, and all others between 2014 and 2020 at Neurology in Ulm, Germany. The samples were examined for different characteristics.

The patient groups were similar for all demographics except for age, where patients with PD were significantly older than controls (P = 0.003), non-ALS (P = 0.03), and ALS (P = 0.04 ) Groups.

NfL and NfH in CSF and serum were significantly increased in patients with ALS compared to control subjects or non-ALS patients (all P <0.0001).

Compared to the other groups, the ALS group had significantly higher CSF-NfL levels compared to PD (P = .03); CSF NfH compared to those with FTLD (P = .0001) and those with AD (P = .004); Serum NfL compared to those with AD (P <.0001) and those with FTLD (P = .04); and serum NfH compared to those with FTLD (P = 0.0008) and those with AD (P = 0.03).

Significant correlations were observed between all 6 biomarker combinations (all P <0.0001); additional correlates included age (all P <.0001) and progression rates in patients with ALS (all P £ .009).

The most effective cutoff rates for differentiating 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.

One of the limitations of the study was the reduced selectivity for the serum NfH variable.

“In summary, we propose here that CSF and serum NfL as well as CSF NfH are equally well suited for the diagnosis and differential diagnosis of ALS,” the researchers write.

Disclosure: Several authors stated links to industry. For a full list of the details, see the original article.

reference

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