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

Abstract

Cerebrospinal fluid neurofilament light and plasma neurofilament light concentrations are elevated in patients with mild cognitive impairment and Alzheimer's disease. We investigated the clinical relevance of increased neurofilament light concentrations in mild cognitive 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 cognitive 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 biomarkers were assessed by Spearman correlation. Linear mixed-effects models were used to test cerebrospinal fluid and plasma neurofilament light as predictors of Alzheimer's disease characteristics, including cognition, cortical glucose metabolism, and brain structure. Cerebrospinal fluid and plasma neurofilament light levels were significantly elevated in Alzheimer's disease. Still, the correlations between neurofilament light and other cerebrospinal fluid biomarkers within the diagnostic groups were often not statistically significant. In addition, the diagnostic accuracy of cerebrospinal fluid and plasma neurofilament light for progressive mild cognitive impairment and Alzheimer's disease was almost the same as that of cerebrospinal fluid total tau (T-tau). It is phosphorylated tau (Ptau) 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 cerebral metabolism, hippocampal atrophy, and ventricular enlargement 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 cognitive impairment and Alzheimer's disease.

Neurofilament light chain concentration mediates the association between regional medial temporal lobe structure and memory in adults with Down syndrome

“…These results are consistent with studies showing that verbal episodic memory is positively associated with hippocampus volume 38 and EC thickness 40 and negatively associated with plasma NfL levels 36 in individuals with DS across the AD spectrum. Plasma NfL levels were negatively correlated with bilateral hippocampus volume and left alEC thickness but not with other EC subregions, in line with findings in neurotypical individuals with and without symptomatic AD 8,41‐43 . In sporadic AD, gray matter loss occurs earlier and progresses faster in the left hemisphere 44 .…”

Neurofilaments Light Chain in Neurodegenerative Dementias: A Review of Imaging Correlates

“…Benedet et al [ 33 ] found that plasma NfLs negatively correlated with frontal and hippocampal GM and fronto-parietal WM volumes in healthy controls, and with wider fronto-temporal GM areas and whole-brain WM volumes in MCI and AD patients, at baseline and over time. Focusing on similar groups of subjects, Chen et al [ 35 ] found that higher CSF NfLs were associated with hippocampal atrophy in MCI patients and controls, and also with ventricular enlargement in AD patients; also, plasma NfLs were associated with the same measures in all the groups.…”

Axonal degeneration serum markers and temporal lobe atrophy in Alzheimer’s dementia continuum: a longitudinal study of plasma neurofilament light and tensor-based morphometry

“…Previous research indicates that NfL is a non-specific marker of neurodegeneration, with increased levels in CSF observed in various dementias [24]. Studies show that elevated levels of NfL in CSF and plasma are linked to AD-related neuroimaging findings, including hippocampal atrophy, ventricular enlargement, and cortical thinning [25][26][27]. Serum NfL levels also increase in healthy aging people and predict brain volume loss [28].…”