Blood neurofilament light: a critical review of its application to neurologic disease

Abstract

Neuronal injury is a universal event that occurs in disease processes that affect both the central and peripheral nervous systems. A blood biomarker linked to neuronal injury would provide a critical measure to understand and treat neurologic diseases. Neurofilament light chain (NfL), a cytoskeletal protein expressed only in neurons, has emerged as such a biomarker. With the ability to quantify neuronal damage in blood, NfL is being applied to a wide range of neurologic conditions to investigate and monitor disease including assessment of treatment efficacy. Blood NfL is not specific for one disease and its release can also be induced by physiological processes. Longitudinal studies in multiple sclerosis, traumatic brain injury, and stroke show accumulation of NfL over days followed by elevated levels over months. Therefore, it may be hard to determine with a single measurement when the peak of NfL is reached and when the levels are normalized. Nonetheless, measurement of blood NfL provides a new blood biomarker for neurologic diseases overcoming the invasiveness of CSF sampling that restricted NfL clinical application. In this review, we examine the use of blood NfL as a biologic test for neurologic disease.

Serum GFAP and NfL as disease severity and prognostic biomarkers in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder

“…2 , Table 1 ) may therefore likewise be related to the long interval between the last attack and blood withdrawal. In contrast, longitudinal studies of patients with multiple sclerosis, traumatic brain injury, and stroke have shown that after increasing over days sNfL levels can remain elevated over months [ 32 ], which appears consistent with the associations of higher sNfL with shorter time to first manifestation of disease and shorter time to last attack in patients with AQP4-IgG + NMOSD and MOG-IgG + patients observed in the present work (Table 3 ). Altogether, our findings underscore a critical role of the timepoint of sGFAP determinations relative to a last attack when interpreting sGFAP values in patients with AQP4-IgG + NMOSD.…”

Serum Neurofilament Light Chain Measurement in MS: Hurdles to Clinical Translation

“…Extensively reviewed elsewhere ( Khalil et al, 2018 ; Barro et al, 2020 ), higher sNfL is seen in many central and peripheral nervous system diseases that involve neuroaxonal injury including neurodegenerative conditions ( Forgrave et al, 2019 ), stroke ( Nielsen et al, 2020 - plasma concentrations), and peripheral neuropathies ( Altmann et al, 2020 ). Analogous to troponin in cardiac disease, clinical context is required.…”

“…For this reason in this review we have chosen to focus on serum as the more prevalent and studied blood biofluid to promote comparability and utility. Otherwise, sNfL has shown good stability over multiple freeze-thaw cycles and prolonged exposure to room temperature (e.g., Hviid et al, 2020 , reviewed by Table 1 in Barro et al, 2020 ).…”

Towards blood biomarkers for stroke patients

“…However, high blood NFL levels are not specific for stroke and its release has been also linked with other neurological conditions including multiple sclerosis and traumatic brain injuries. 8 Therefore, stroke patients and clinicians may further benefit from recent advancements in the development of risk prediction and diagnostic biomarkers. Increased search for novel blood biomarker after stroke also revealed other promising candidates e.g.…”