Plasma neurofilament light associates with Alzheimer's disease metabolic decline in amyloid-positive individuals

INTRODUCTION: Neurofilament light chain (NfL) is a promising blood biomarker to detect neurodegeneration in Alzheimer's disease (AD) and other brain disorders. However, there are limited reports of how longitudinal NfL relates to imaging biomarkers. We herein investigated the relationship between blood NfL and brain metabolism in AD. METHODS: Voxelwise regression models tested the cross-sectional association between [(18)F]fluorodeoxyglucose ([(18)F]FDG) and both plasma and cerebrospinal fluid NfL in cognitively impaired and unimpaired subjects. Linear mixed models were also used to test the longitudinal association between NfL and [(18)F]FDG in amyloid positive (Aβ+) and negative (Aβ−) subjects. RESULTS: Higher concentrations of plasma and cerebrospinal fluid NfL were associated with reduced [(18)F]FDG uptake in correspondent brain regions. In Aβ+ participants, NfL associates with hypometabolism in AD-vulnerable regions. Longitudinal changes in the association [(18)F]FDG-NfL were confined to cognitively impaired Aβ+ individuals. DISCUSSION: These findings indicate that plasma NfL is a proxy for neurodegeneration in AD-related regions in Aβ+ subjects.