Serum Neurofilament light correlates with CADASIL disease severity and survival

• Published in: Annals of clinical and translational neurology 2019-01, Vol.6 (1), p.46-56
• Main Authors: Gravesteijn, Gido, Rutten, Julie W., Verberk, Inge M. W., Böhringer, Stefan, Liem, Michael K., Grond, Jeroen, Aartsma‐Rus, Annemieke, Teunissen, Charlotte E., Lesnik Oberstein, Saskia A. J.
• Format: Article
• Language: English
• Subjects: Adult; Age; Atrophy; Biomarkers; Biomarkers - blood; Brain research; CADASIL - blood; CADASIL - diagnosis; CADASIL - pathology; Clinical trials; Consent; Cross-Sectional Studies; Disease Progression; Family medical history; Female; Humans; Kaplan-Meier Estimate; Male; Medical imaging; Mutation; Neurofilament Proteins - blood; Patients; Sensitivity and Specificity; Severity of Illness Index; Stroke; Studies
• ISSN: 2328-9503; 2328-9503
• DOI: 10.1002/acn3.678

Objective To validate whether serum Neurofilament Light‐chain (NfL) levels correlate with disease severity in CADASIL, and to determine whether serum NfL predicts disease progression and survival. Methods Fourty‐one (pre‐) manifest individuals with CADASIL causing NOTCH3 mutations and 22 healthy controls were recruited from CADASIL families. At baseline, MRI‐lesion load and clinical severity was determined and serum was stored. Disease progression was measured in 30/41 patients at 7‐year follow‐up, and survival of all individuals was determined at 17‐year follow‐up. Serum NfL levels were quantified using an ultra‐sensitive molecule array. Generalized estimated equation regression (GEE) was used to analyze association between serum NfL, MRI‐lesion load, disease severity, and disease progression. With GEE‐based Cox regression, survival was analyzed. Results At baseline, serum NfL levels correlated with MRI‐lesion load [lacune count (s = 0.64, P = 0.002), brain atrophy (r = −0.50, P = 0.001), and microbleed count (s = 0.48, P = 0.044)], cognition [CAMCOG (s = −0.45, P = 0.010), MMSE (r = −0.61, P = 0.003), GIT (r = −0.61, P