Serial measurements of phosphorylated neurofilament-heavy in the serum of subjects with amyotrophic lateral sclerosis

Abstract

There is a need for a blood biomarker of disease activity in ALS. This marker needs to measure the loss of motor neurones. Phosphorylated neurofilament heavy chain (pNfH) in the serum is a biomarker of axonal injury. Previous studies have found that levels of pNfH are elevated in ALS. We have performed a serial study of pNfH levels in 98 subjects from our ALS clinic. There was significant elevation of levels of pNfH in subjects with ALS compared to controls, although there was considerable variability. In studies of individuals who had two or more serial samples, we found that the levels of pNfH increased over time in the early stage of disease. Levels were low in subjects with long survival. The rate of rise of pNfH was inversely correlated with survival. We suggest that the initial level of pNfH is a marker of disease severity and that changes in pNfH levels are markers of disease progression.

Fluid-Based Biomarkers for Amyotrophic Lateral Sclerosis

“…Recent longitudinal studies examining pNFH in CSF or blood show relatively stable levels over time, though levels of pNFH in serum appeared to increase at early stages of the disease [34,43]. Weydt et al measured levels of pNFH and NFL in CSF and blood of symptomatic and asymptomatic carriers of disease causing mutations to determine if either biomarker could be detected in symptomatic individuals [44].…”

Clinical and laboratory features of ALS

“…There was no significant difference in levels of NFH between patients treated with Riluzole and those without [173] . Bulbar onset patients were reported to have elevated concentration of NFH in plasma compared with spinal onset patients [175] .…”

“…There is significant difference between the two groups (P< 0.0001) Symptomatic ALS gene mutation carriers had significantly increased blood levels of NFL compared to asymptomatic carriers of causative mutations [167] . There were no differences in the blood NFL level between ALS patients treated with Riluzole and those without [173] . Three papers found that there was a high correlation of NFL levels between CSF and serum and/or plasma [167,178,179] .…”

“…The NFH meta-analysis between healthy controls/controls without parenchymal CNS involvement and ALS patients in blood was based on 2 studies [173,174] including 78 healthy controls and 117 patients ( Figure 5). The concentration of NFH in the ALS patients group was not significantly increased relative to the healthy controls/ without CNS involvement (P =0.068).…”

“…There is correlation of pNFH between CSF and blood levels of NFH [172] . Two papers reported that the concentration of NFH in the blood showed an initial rise but later the levels fell [173,175] 3.3.4 NFL levels in CSF…”