Neurofilament Light Chain: A potential biomarker for cerebrovascular disease in children with sickle cell anemia

Abstract

Cerebrovascular injury frequently occurs in children with sickle cell anaemia (SCA). Limited access to magnetic resonance imaging and angiography (MRI-MRA) in sub-Saharan Africa impedes detection of clinically unapparent cerebrovascular injury. Blood-based brain biomarkers of cerebral infarcts have been identified in non-SCA adults. Using plasma samples from a well-characterized cross-sectional sample of Ugandan children with SCA, we explored relationships between biomarker levels and MRI-detected cerebral infarcts and transcranial Doppler (TCD) arterial velocity. Testing was performed using a 4-plex panel of brain injury biomarkers, including neurofilament light chain (NfL), a central nervous system neuron-specific protein. Mean biomarker levels from the SCA group (n = 81) were similar to those from non-SCA sibling controls (n = 54). Within the SCA group, NfL levels were significantly higher in those with MRI-detected infarcts compared to no infarcts, and higher with elevated TCD velocity versus normal velocity. Elevated NfL remained strongly associated with MRI-detected infarcts after adjusting for sex and age. All non-SCA controls and SCA participants lacking MRI-detected infarcts had low NfL levels. These data suggest potential utility of plasma-based NfL levels to identify children with SCA cerebrovascular injury. Replication and prospective studies are needed to confirm these novel findings and the clinical utility of NfL versus MRI imaging.