ASSOCIATION OF PLASMA NEUROFILAMENT LIGHT CHAIN PROTEIN WITH BRAIN AMYLOID STATUS IN A PRECLINICAL COHORT OF SUBJECTIVE MEMORY COMPLAINERS: THE INSIGHT-PREAD STUDY

Abstract

Cerebrospinal fluid (CSF) neurofilament light chain (NFL) protein has been shown to be a biomarker of large-caliber myelinated axonal disintegration, a pathophysiological mechanism associated with Alzheimer disease (AD). Since early detection of AD pathophysiology in blood samples is minimally invasive and potentially offers extensive and low-cost population screening, we assessed the association of plasma NFL concentrations with brain amyloid status in a preclinical cohort of cognitively normal subjects with subjective memory complaints. The INSIGHT-preAD study – a mono-centric French cohort established at the Pitié-Salpêtrière University Hospital in Paris with the goal to investigate the earliest preclinical stages of AD and its development – includes 318 cognitively normal Caucasian individuals, between 70–85 years old, with subjective memory complaints and with a defined brain amyloid status at baseline (T0). All subjects agreed to participate in a 5-year follow-up. Demographic, cognitive, functional, nutritional, biological, genetic, genomic, imaging, electrophysiological and other assessments were performed at T0. The mean age of the subjects was 76.1 (± 3.5) with a Mini-Mental State Examination (MMSE) score of 28.7 (± 0.95) and a predominance of females (62.9%). All subjects had a normal total recall at the Free and Cued Selective Reminding Test (FCRST) (mean 46.1 ± 2.0). When using a cutoff of 0.88, the amyloid-positive subgroup consisted of 64 subjects (27.7%). Plasma NFL concentrations were not significantly different in the amyloid-positive subgroup (31.26 ± 12.51 pg/mL) compared with the amyloid-negative subgroup (29.62 ± 12.89 pg/mL) (P=0.270). Plasma NFL concentrations did not significantly correlate with the mean cortical uptake of 18F-florbetapir. In this cross-sectional study, plasma NFL was not associated with brain amyloid status in individuals with subjective memory complaints. Data from ongoing longitudinal clinical follow-up will tell whether plasma NFL may predict future cognitive decline.