Serum NfL could serve as a biomarker in spinocerebellar ataxia type 1
By Shreeya Nanda, medwireNews Reporter
Serum levels of neurofilament light (sNfL) protein are elevated in both the pre-ataxic and ataxic stages of spinocerebellar ataxia type 1 (SCA1), and are associated with onset of ataxia, shows research published in Neurology.
Carlo Wilke (University of Tübingen, Germany) and co-investigators therefore believe that sNfL levels could serve as an easily assessable biomarker “in both preataxic and ataxic SCA1, allowing stratification of preataxic subjects regarding proximity-to-onset, early detection of neurodegeneration even before volumetric MRI [magnetic resonance imaging] alterations, and potentially capture of treatment response in clinical trials.”
The study cohort included 40 individuals with genetically confirmed SCA1 (ATXN1 repeat length ≥39) and 89 healthy controls drawn from the EUROSCA and RISCA projects as well as from the University of Tübingen. On the basis of the Scale for the Assessment and Rating of Ataxia, 23 of the SCA1 participants were classified as pre-ataxic (<3 points) and 17 as ataxic (≥3 points) at baseline, with 11 pre-ataxic individuals converting to the ataxic stage during longitudinal follow-up (median sampling interval, 2.7 years).
sNfL concentrations were significantly increased in both pre-ataxic and ataxic SCA1 participants relative to healthy controls, at medians of 15.5 and 31.6 pg/mL versus 6.0 pg/mL, respectively.
The effect sizes were high for both the pre-ataxic and ataxic stages after correcting for age-related sNfL increases (correlation coefficients=0.62 and 0.63, respectively), and the increases paralleled those of NfL levels in cerebrospinal fluid, say the researchers.
In pre-ataxic participants, sNfL levels rose significantly with proximity to the individually predicted onset of ataxia as well as to the observed onset among those who converted to the ataxic stage during follow-up. The levels were significantly elevated versus controls 5 years before the predicted onset and 4 years before the observed onset.
Finally, Wilke and colleagues analysed sNfL concentrations in 12 pre-ataxic participants with available volumetric MRI data, nine of whom did not show any evidence of pontine or cerebellar atrophy.
Even in this latter subset, sNfL levels were significantly higher than those of controls (median, 16.7 vs 6.0 pg/mL), “thus suggesting that the sNfL increase in blood might precede not only clinical onset, but also pontine and cerebellar volumetric atrophy, which are considered the earliest and most change-sensitive volumetric MRI changes in SCA1”, they write.
The study authors say that “additional longitudinal measurements of NfL levels during the preataxic stage are needed to model the early intra-individual dynamics of NfL levels in SCA1 in more detail”, and they also highlight the need for validation of these results “in independent larger multicentric cohorts of SCA1 subjects, like the READISCA cohort.”
Nevertheless, Wilke et al believe that their study represents the “first steps towards a multimodal biomarker-based stratification of the preataxic disease stage of SCA1.”
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Neurology 2022; doi:10.1212/WNL.0000000000200257