O3‐09‐02: correlation and longitudinal dynamics of plasma nfl and tau concentrations in amyloid‐pet negative individuals with subjective memory complaints

Plasma neurofilament light chain (NFL) is a biomarker of large caliber myelinated axonal disruption, a key pathophysiological mechanism associated with several neurodegenerative diseases, including Alzheimer disease (AD). Few studies investigated the dynamics of plasma NFL concentrations during the preclinical stage of AD. The objective of the study is to explore the temporal dynamics of plasma NFL concentrations in a cohort of individuals with subjective memory complaints (SMC) at risk of AD, stratified by Aβ deposition. Cross-sectional and longitudinal large-scale investigation of, SMC (N=316 and N=79, respectively) of the French monocentric INSIGHT-preAD cohort established at the Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France. All subjects underwent amyloid-PET (Aβ-PET) scanning, time series (three-time points within a 2-year follow-up) for plasma NFL concentrations measured using an in house Single molecule array assay, and other plasma markers (BACE1, Aβ1-42, Aβ1-40, t-tau, YKL-40). Participants were stratified into Aβ-PET+ and Aβ-PET. We investigated differences of NFL concentrations according to the Aβ-PET status, APOE genotype, sex and age. Then, we investigated the associations of NFL with Aβ-PET regional/global SUVR and with other plasma markers taking into account age and sex as covariates. At baseline, plasma NFL concentrations did not significantly change in terms of sex, APOE, and Aβ-PET status. Baseline plasma NFL concentrations correlated with age in the whole sample (R2= 0.069, p<0.001). Plasma NFL concentrations showed increased over time (T1 versus T2 p=0.0016, T2 versus T3 p<0.001, T1 versus T3 p<0.001, respectively). Exclusively in the Aβ-PET- group, NFL correlated with Tau both at cross-sectional and longitudinal level (r=0.218, p=0.001; r=0.300, p=0.003 respectively). We found an effect of time on the difference of the mean between NFL and Tau (ANOVA 2-way, p<0.001). Plasma NFL concentrations in SMC individuals seem to be associated with age and show a general increase overtime. Furthermore, plasma NFL concentrations are not affected by sex, APOE status, and in vivo brain amyloid load. Finally, the positive correlation of plasma NFL with Tau in AβPET- indicates the existence of non-AD pathophysiology highlighting neurodegenerative mechanisms in SMC.