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DOI: 10.1101/2023.05.19.23290183

Plasma neurofilament light chain predicts Alzheimer's disease in patients with subjective cognitive decline and mild cognitive impairment: a longitudinal study

S.Mazzeo S. Bagnoli A. Ingannato ...+16 V. Bessi
Background: We aimed to evaluate the accuracy of plasma neurofilament light chain (NfL) in predicting Alzheimer's disease (AD) and the progression of cognitive decline in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). Methods: This longitudinal cohort study involved 140 patients (50 with SCD, 73 with MCI, and 22 with AD dementia [AD-D]) who underwent plasma NfL and AD biomarker assessments (CSF, amyloid-PET, and 18F-FDG-PET) at baseline. They were rated according to the A/T/N system and followed up for a mean time of 2.72{+/-}0.95 years to detect progression from SCD to MCI and from MCI to AD. Forty-eight patients (19 SCD, 29 MCI) also underwent plasma NfL measurements after two years after baseline. Results: At baseline, plasma NfL detected patients with biomarker profiles consistent with AD (A+/T+/N+ or A+/T+/N-) with high accuracy (AUC=0.82). We identified cut-off value of 19.45 pg/mL for SCD and 20.45 pg/mL for MCI. During follow-up, nine SCD patients progressed to MCI (p-SCD), and 14 MCI patients developed AD dementia (p-MCI). The previously identified cut-off values provided good accuracy in identifying p-SCD (80% [95% C.I.=65.69:94.31]). The rate of NfL change was higher in p-MCI (3.52{+/-}4.06 pg/mL) compared to np-SCD (0.81{+/-}1.25 pg/mL) and np-MCI (-0.13{+/-}3.24 pg/mL) patients. A rate of change lower than 1.64 pg/mL per year accurately excluded progression from MCI to AD (AUC=0.954). Conclusion: Plasma NfL concentration and change over time may be a reliable, non-invasive tool to detect AD and the progression of cognitive decline at the earliest stages of the disease.