Reader response: Serum neurofilament light is sensitive to active cerebral small vessel disease

The study by Gattringer et al.¹ of symptomatic patients with a recent small subcortical infarct revealed a dynamic relationship between serum neurofilament light chain (NfL) and microangiopathic MRI changes emphasizing NfL’s pivotal role as a new biomarker of active cerebral small vessel disease (CSVD), even if clinically silent. We confirm and extend the authors’ findings of CSF NfL by studying an incident chronic CSVD cohort selected through the presence of microhemorrhages (n = 14).² Compared to controls (n = 33), patients with CSVD displayed significantly higher CSF NfL concentrations (mean [SD] 1.318 [491] vs 11.068 [13.031] pg/mL, F₁ = 8.4, p = 0.006), within the range found in amyotrophic lateral sclerosis (12.016 [9.943] pg/mL, n = 99, F₁ = 0.1, p = 0.7), where increased CSF NfL is already established as a diagnostic biomarker of neuroaxonal injury.³ In chronic CSVD, there was a relationship between CSF NfL, peribasal ganglia white matter hyperintensities (r = 0.5, p = 0.02),⁴ and lacunes (r = 0.5, p = 0.04). Our data support the idea of NfL reflecting CSVD burden. Neurofilaments may also serve as a prognostic/disease activity biomarker in terms of predicting stroke and dementia development.