Longitudinal Measurement of Serum Neurofilament Light Chain in Patients With CADASIL

In sporadic cerebral small vessel disease (SVD), blood neurofilament light chain (NfL) has been associated with disease severity and activity in cross-sectional studies.Baseline blood NfL levels were predictive of cognitive decline and dementia development in longitudinal studies. [1]2][3] Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CA-DASIL) is the most common hereditary cerebral SVD and is caused by mutations in the NOTCH3 gene.Moreover, blood NfL levels are associated with magnetic resonance imaging (MRI) markers of CADASIL-induced cerebral SVD, cognitive deficits, and disability. 1,4,5 However, our knowledge of the longitudinal change in blood NfL levels in patients with SVD is limited due to the small number of such studies. 6,7 In CADASIL, SVD has an early onset, occurring even in patients in their 20s, and significant changes are seen even after only 3 years of follow-up. 8,9 Disease progression is known to vary widely among patients with CADASIL. 10 Therefore, CADASIL could be a useful target for investigating longitudinal changes.In this study, we measured serum NfL levels at baseline and after 3 years to investigate the clinical significance of longitudinal changes in serum NfL levels in patients with CADASIL.This was a single-center prospective study.We consecutively enrolled patients with CADASIL who were followed up regularly in the outpatient clinic at Jeju National University Hospital, Jeju, South Korea, from October 2018 to October 2019.We assessed clinical symptoms, cognitive function, brain MRI findings, and serum NfL levels at baseline and after a 3-year follow-up.We