**6. Conclusions**

Measurement of a convenient objective blood marker of neuronal injury in patients is an appealing prospect for neurologists. Analogous to the cardiologist's troponin, neurofilament light chain is a structural axonal protein that can be detected in the blood at elevated levels in a variety of neurological disease states which can be followed longitudinally. Enabled by recent advancements in assay technologies, many consider this test to be on the verge of clinical translation in a number of di fferent settings. Given its neuron-specific nature, but lack of disease specificity, on its own it is not a helpful diagnostic marker. However, in defined neurological conditions that require monitoring, in particular MS where we have treatments to o ffer, NfL is rapidly gaining traction.

It seems likely that MS will represent the test case for the clinical translation of blood NfL, where it will be a greatly-needed adjunct to clinical and MRI assessment. While we already know that elevated NfL is concerning and low NfL is reassuring, a number of challenges remain before this test is ready for widespread adoption. Foremost amongs<sup>t</sup> them is the need for age-adjusted normative datasets and cuto ff values so that physicians can better interpret individual patient results. Key elements of neurofilament kinetics in the blood, such as blood half-life, need to be delineated to inform optimal testing frequency in clinical practice. Additionally, the ongoing e fforts of multisite validation e fforts will be important in standardising measurement between clinical laboratories and ensuring that any concerns of analytical validity are allayed. Nonetheless, many are optimistic that NfL could represent the first of its kind in neurology: a broadly-applicable protein biomarker that objectively reflects underlying pathology which can be harnessed to improve patient outcomes.

**Author Contributions:** S.T.: conceptualization, literature review and writing—original draft preparation, reviewing and editing, R.A.B. and M.S.F.: conceptualization, writing—reviewing and editing, supervision. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Conflicts of Interest:** The authors declare no conflict of interest.
