Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration | October 3, 2023

Ulf Kläppe, Stefan Sennfält, Anikó Lovik, Anja Finn, Ulrika Bofaisal, Henrik Zetterberg, Kaj Blennow, Fredrik Piehl, Ivan Kmezic, Rayomand Press, Kristin Samuelsson, Anna Månberg, Fang Fang & Caroline Ingre

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2023

https://doi.org/10.1080/21678421.2023.2263874

Abstract

Objective

To describe the diagnostic and prognostic performance, and longitudinal trajectories, of potential biomarkers of neuroaxonal degeneration and neuroinflammation in amyotrophic lateral sclerosis (ALS).

Methods

This case-control study included 192 incident ALS patients, 42 ALS mimics, 114 neurological controls, and 117 healthy controls from Stockholm, Sweden. Forty-four ALS patients provided repeated measurements. We assessed biomarkers of (Citation1)neuroaxonal degeneration: neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in cerebrospinal fluid (CSF) and NfL in serum, and (Citation2)neuroinflammation: chitotriosidase-1 (CHIT1) and monocyte chemoattractant protein 1 (MCP-1) in CSF. To evaluate diagnostic performance, we calculated the area under the curve (AUC). To estimate prognostic performance, we applied quantile regression and Cox regression. We used linear regression models with robust standard errors to assess temporal changes over time.

Results

Neurofilaments performed better at differentiating ALS patients from mimics (AUC: pNfH 0.92, CSF NfL 0.86, serum NfL 0.91) than neuroinflammatory biomarkers (AUC: CHIT1 0.71, MCP-1 0.56). Combining biomarkers did not improve diagnostic performance. Similarly, neurofilaments performed better than neuroinflammatory biomarkers at predicting functional decline and survival. The stratified analysis revealed differences according to the site of onset: in bulbar patients, neurofilaments and CHIT1 performed worse at predicting survival and correlations were lower between biomarkers. Finally, in bulbar patients, neurofilaments and CHIT1 increased longitudinally but were stable in spinal patients.

Conclusions

Biomarkers of neuroaxonal degeneration displayed better diagnostic and prognostic value compared with neuroinflammatory biomarkers. However, in contrast to spinal patients, in bulbar patients neurofilaments and CHIT1 performed worse at predicting survival and seemed to increase over time.