Abstract
Abstract only Introduction: The Neurofilament light chain (NfL) is a neuronal cytoplasmic protein and a reliable biomarker for assessing axonal damage in neurological diseases and traumatic brain injury. Asymptomatic intracranial large artery stenosis (ILAS) has been associated with higher risk of stroke and dementia. Although widely studied in the last few years, the role of NfL concentrations in ILAS is not well understood. Methods: We leveraged data from stroke-free participants in the population-based cohort Northern Manhattan Study (NOMAS) for a pilot study. Arterial stenosis was measured on magnetic resonance angiography in 11 intracranial large arteries and graded as 0 = no stenosis, 1 ≤ 50%, 2 = 50-69%, 3 ≥ 70% stenosis and 4 = flow gap. An asymptomatic Intracranial Large Artery Stenosis (ILAS) score was then developed to reflect the global stenotic burden, with a range of 0 to 44. We also dichotomized the ILAS score into any stenosis > 50% versus none to reflect a more clinically relevant definition of ILAS. NfL concentrations were measured in plasma using Quanterix Simoa™ platform. We conducted generalized linear models adjusting for demographic and vascular risk factors and Wald Chi-Square test to analyze the association between NfL and ILAS score. Results: We included 79 stroke-free NOMAS participants (66% women, 77% Hispanic/Latino, and 75% with hypertension). The mean concentration of NFL was 0.19±0.10 pg/mL with a mean intra-assay coefficient of variation equal to 8.2%. In a model adjusted for age, sex, race/ethnicity, hypertension, diabetes, dyslipidemia and smoking, a higher ILAS score was associated with increased levels of NfL (B=0.01 ± 0.004, p=0.007). In an adjusted model, any stenosis >50% was also associated with increased levels of NfL (B=0.11 ± 0.03, p<0.001). Conclusions: The increased levels of plasma NfL associated with asymptomatic ILAS suggest neuronal injury that may implicate development of neurodegeneration. Confirming these results in a larger sample and longitudinal evaluation of NfL may advance the understanding of the mechanisms by which ILAS may increase the risk of dementia.