NfL and pNfH are increased in Friedreich’s ataxia

Abstract

Objective To assess neurofilaments as neurodegenerative biomarkers in serum of patients with Friedreich's ataxia. Methods Single molecule array measurements of neurofilament light (NfL) and heavy chain (pNfH) in 99 patients with genetically confirmed Friedreich's ataxia. Correlation of NfL/pNfH serum levels with disease severity, disease duration, age, age at onset, and GAA repeat length. Results Median serum levels of NfL were 21.2 pg/ml (range 3.6-49.3) in controls and 26.1 pg/ml (0-78.1) in Friedreich's ataxia (p = 0.002). pNfH levels were 23.5 pg/ml (13.3-43.3) in controls and 92 pg/ml (3.1-303) in Friedreich's ataxia (p = 0.0004). NfL levels were significantly increased in younger patients (age 16-31 years, p < 0.001) and patients aged 32-47 years (p = 0.008), but not in patients of age 48 years and older (p = 0.41). In a longitudinal assessment, there was no difference in NfL levels in 14 patients with repeated sampling 2 years after baseline measurement. Levels of NfL correlated inversely with GAA1 repeat length (r = − 0.24, p = 0.02) but not with disease severity (r = − 0.13, p = 0.22), disease duration (r = − 0.06, p = 0.53), or age at onset (r = 0.05, p = 0.62). Conclusion Serum levels of NfL and pNfH are elevated in Friedreich's ataxia, but differences to healthy controls decrease with increasing age. Long-term longitudinal data are required to explore whether this reflects a selection bias from early death of more severely affected individuals or a slowing down of the neurodegenerative process with age. In a pilot study over 2 years of follow-up-a period relevant for biomarkers indicating treatment effects-we found NfL levels to be stable.

Neurofilament light chain is a cerebrospinal fluid biomarker in hereditary spastic paraplegia

“…The higher rate of age‐related annual cNfL increase in controls compared to HSP patients may further indicate a declining number of upper motor neuron axons in HSP cases as the source of cNfL as the disease progresses. Similar temporal dynamics of sNfL have recently been described in Spinocerebellar ataxia type 3 (SCA3) 20 and Friedreich’s ataxia, 21 representing two other slowly progressive neurodegenerative disorders. The temporal dynamics of NfL over the disease course, here deduced from cohort‐based analyses, will have to be confirmed in serial measurements of NfL in HSP patients.…”

Different Clinical Contexts of Use of Blood Neurofilament Light Chain Protein in the Spectrum of Neurodegenerative Diseases

“…However, no differences were observed between early preclinical subjects and HC [167]. Despite CAG repeat count is a well-known prognostic factor for SCA-3 and FA, a correlation between serum NFL and CAG repeat lengths has been inconsistently reported [168,169].…”

“…F associated with worse survival (Table 2) [164]. Higher baseduration [169]. Moreover, serum NFL concentration remains stable in a subgroup of 14 FA patients who received a 2-year follow-up evaluation [169].…”

Neurological symptoms and blood neurofilament light levels

“…Multiple system atrophy, an adult‐onset neurodegenerative ataxia, was associated with increased NfL levels and NfL showed a good sensitivity and specificity in identifying this condition from ataxia of sporadic onset 45 . NfL was also increased in forms of ataxia with a genetic background as Friedreich's ataxia 46 and spinocerebellar ataxias 47 . Cerebellar stroke can also manifest with ataxia and is associated with increased NfL levels 9 .…”