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 (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 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.
Highlights
Alzheimer’s disease (AD) is the main cause of dementia, which is characterized by extracellular accumulation of aggregated β-amyloid (Aβ), intracellular aggregation of hyperphosphorylated tau, and synaptic dysfunction [1, 2]
Apolipoprotein E (APOE) ε4 carriership was more common in AD than cognitively normal (CN) and sMCI and more common in pMCI than CN
Cerebrospinal fluid (CSF) neurofilament light chain (NFL) concentrations in pMCI and AD were higher than that in CN (p < 0.05), and CSF NFL levels in AD were higher than that in sMCI (p < 0.05), but there was no significant difference between pMCI and AD, and between sMCI and pMCI (Fig. 1A)
Summary
Alzheimer’s disease (AD) is the main cause of dementia, which is characterized by extracellular accumulation of aggregated β-amyloid (Aβ), intracellular aggregation of hyperphosphorylated tau, and synaptic dysfunction [1, 2]. Cerebrospinal fluid (CSF) Aβ42 and tau have been used to diagnose AD and monitor disease progression [8]. Other biomarkers have been confirmed to further characterize the pathophysiological process of AD [9]. In CSF, neurofilament proteins (cytoskeletal protein of neurons), including neurofilament light chain (NFL), were associated with axonal degeneration in various diseases, including AD [12]. Several reports have suggested that CSF NFL are elevated early in the AD process and are associated with longitudinal neurodegeneration and cognitive decline [13]. Recent studies have demonstrated that concentrations of NFL derived from plasma were elevated in patients with AD and related to CSF Aβ and tau and positron emission tomography (PET) [14,15,16]
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