Neurofilament light protein and risk of mild cognitive impairment

BACKGROUND AND OBJECTIVE Prognostic markers for Alzheimer′s disease have included cerebral spinal fluid amyloid-beta 42 (Aβ-42), total tau (T-Tau) and phosphorus related tau (P-Tau). Two more recently identified biomarkers are neurofilament light protein (NFL) and neurogranin (NG). NFL is thought to be a marker for subcortical largecaliber axonal degeneration, while NG is believed to be a biomarker for synaptic dysfunction and/or loss. This study investigated whether cerebral spinal fluid levels of NFL and NG are biomarkers of mild cognitive impairment (MCI). METHODS Subjects were a subset of participants in the Mayo Clinic Study of Aging. Data were obtained from 648 individuals without cognitive impairment, all with at least one year of follow-up with cognitive testing. Cerebral spinal fluid was taken by lumbar puncture, with AB42, T-tau, Ptau, NFL and NG measured. The CSF results were compared with the development of MCI at follow-up. RESULTS Data were obtained for 648 patients with an average age of 72.3 years. At a median follow-up of 3.8 years, 14.8% progressed to MCI. Those who progressed to MCI were more frequently carriers of an APOE epsilon allele (P=0.02). Compared with the lowest quartile of CSF NFL, the highest quartile was associated with a 2.9-fold increased risk of MCI. There was no significant association between increased CSF T-Tau, PTau or NG and the risk of MCI. CONCLUSION This prospective study of community dwelling, elderly individuals without cognitive impairment found that elevated levels of neurofilament light protein in the cerebrospinal fluid are associated with an increased risk of developing mild cognitive impairment.