Plasma neurofilament light chain predicts Alzheimer’s pathology and progression of cognitive decline in patients with subjective cognitive decline and mild cognitive impairment: a longitudinal study
Salvatore Mazzeo1, Silvia Bagnoli1, Sonia Padiglioni2, Giulia Giacomucci1, Assunta Ingannato1, Filippo Emiliani1, Valentina Moschini2, Giulia Galdo1, Carmen Morinelli2, Sandro Sorbi3, Benedetta Nacmias1, Valentina Bessi2
1Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, 2Research and Innovation Centre for Dementia - CRIDEM, Careggi University Hospital, 3IRCCS Don Carlo Gnocchi Foundation
Objective:
To evaluate the accuracy of plasma neurofilament light chain in predicting Alzheimer’s disease biomarker status and progression of cognitive decline in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI).
Background:
NfL is a non-specific marker of neurodegeneration. In a previous cross-sectional study, we demonstrated that plasmatic NfL levels change as a function of Aβ status.
Design/Methods:
119 patients (35 SCD, 59 MCI, and 25 AD) underwent plasma NfL and CSF biomarker measurement at baseline. They were rated according to the A/T(N) system (Jack et al., 2016) and classified as carriers of the AD pathology (AP+) when A+ was associated with either T+ or N+, or non-carriers (AP–) when they were rated as A– (regardless of T and N classification), or as A+/T-/N-. 38 patients had plasma NfL measurement after two years from baseline collection.
Results:
NfL levels were significantly different between SCD, MCI and AD. NfLs were higher in AP+ as compared to AP– (p<0.001), both in SCD and MCI groups. We identified a cut-off of 20.40 pg/mL to distinguish between AP– and AP+ with a high accuracy (AUC = 0.84) and a very high positive predictive value (91.67%). During the follow-up, NfLs levels increased by 0.63 and 1.13 pg/mL per year in AP– and AP+ patients respectively. Interestingly, mean NfL level in AP– patients never significantly exceed 20 pg/mL. Moreover, five SCDs (14.28%) progressed to MCI and eleven MCIs (18.64%) progressed to AD. NfL showed a very high negative predictive value in estimating the odds of progression to MCI (95.83%) and to AD (88.89%) by applying 20.40 pg/mL as cut-off value.
Conclusions:
NfL is not specific for AD. Nevertheless, if applied on on a selected population (patients with memory complaint or impairment without other possible causes), NfL is a reliable, non-invasive tool to detect Alzheimer’s pathology at the earliest stages.