Neurofilament light as a biomarker of axonal degeneration in patients with mild cognitive impairment and Alzheimer's disease

Cerebrospinal fluid neurofilament light and plasma neurofilament light concentrations are elevated in patients with mild cognitive im-pairment and Alzheimer's disease. We investigated the clinical rele-vance of increased neurofilament light concentrations in mild cog-nitive impairment and Alzheimer's disease patients. In this study, 244 subjects were divided into cognitively normal control (n = 67), stable mild cognitive impairment (n = 52), progressive mild cogni-tive impairment (n = 68), and Alzheimer's disease (n = 57). Linear regression examined the relationships between neurofilament light levels in cerebrospinal fluid or plasma and the diagnostic group. The relationships between neurofilament light and other biomark-ers were assessed by Spearman correlation. Linear mixed-effects models were used to test cerebrospinal fluid and plasma neurofil-ament light as predictors of Alzheimer's disease characteristics, in-cluding cognition, cortical glucose metabolism, and brain structure. Cerebrospinal fluid and plasma neurofilament light levels were sig-nificantly elevated in Alzheimer's disease. Still, the correlations be-tween neurofilament light and other cerebrospinal fluid biomark-ers within the diagnostic groups were often not statistically signif-icant. In addition, the diagnostic accuracy of cerebrospinal fluid and plasma neurofilament light for progressive mild cognitive im-pairment and Alzheimer's disease was almost the same as that of cerebrospinal fluid total tau (T-tau). It is phosphorylated tau (P-tau) and high cerebrospinal fluid. Neurofilament light predicted conversion from mild cognitive impairment to Alzheimer's disease. A high neurofilament light is related to poor cognition, low cere-bral metabolism, hippocampal atrophy, and ventricular enlarge-ment caused by Alzheimer's disease. Our work further identifies cerebrospinal fluid neurofilament light and plasma neurofilament light as biomarkers of axonal degeneration in patients with mild cog-nitive impairment and Alzheimer's disease.