A Longitudinal Examination of Plasma Neurofilament Light and Total Tau for the Clinical Detection and Monitoring of Alzheimer’s Disease

Abstract We examined baseline and longitudinal associations between plasma neurofilament light (NfL) and total tau (t-tau), and the clinical presentation of Alzheimer’s disease (AD). 579 participants (238, normal cognition [NC]; 185, mild cognitive impairment [MCI]; 156, AD dementia) had baseline blood draws; 82% had follow-up evaluations. Plasma samples were analyzed for NfL and t-tau using Simoa technology. Baseline plasma NfL was higher in AD dementia compared to MCI (standardized mean difference=0.55, 95% CI: 0.37-0.73) and NC (standardized mean difference=0.68, 95% CI: 0.49-0.88), corresponded to CDR scores (OR=1.94, 95% CI: 1.35-2.79]), and correlated with all neuropsychological tests (r’s=0.13-0.42). Longitudinally, NfL did not predict diagnostic conversion, but predicted decline on 3/10 neuropsychological tests. Baseline plasma t-tau was higher in AD dementia compared to NC with a small effect (standardized mean difference=0.33, 95% CI: 0.10-0.57) but not MCI. T-tau did not statistically significant predict any longitudinal outcomes. Plasma NfL may be useful for the detection of AD dementia and monitoring of disease progression. In contrast, there was minimal evidence in support of plasma t-tau.