To investigate whether baseline concentrations of plasma total tau (t-tau) and neurofilament light (NfL) chain proteins are associated with annual percent change (APC) of the basal forebrain cholinergic system (BFCS) in cognitively intact older adults at risk for Alzheimer disease (AD).
We analyzed 5 validated pathophysiological cerebrospinal fluid biomarkers (Aβ<sub>1-42</sub>, t-tau, p-tau<sub>181</sub>, NFL, YKL-40) in 113 participants (healthy controls [N = 20], subjective memory complainers [N = 36], mild cognitive impairment [N = 20], and AD dementia [N = 37], age: 66.7 ± 10.4, 70.4 ± 7.7, 71.7 ± 8.4, 76.2 ± 3.5 years [mean ± SD], respectively) using Density-Based Spatial Clustering of Applications with Noise, which does not require a priori determination of the number of clusters.
Plasma neurofilament light chain (NfL) is one of the established biomarkers of AD, suggesting that it may be useful as an indicator of dementia in DS patients.
Neurofilament light (NF-L) is a surrogate marker in plasma and cerebrospinal fluid (CSF) for neurodegeneration (Abu-Rumeileh et al., Alzheimers Res Ther 10: 3, 2018; Mattsson et al., JAMA Neurol 74: 557-566, 2017) but continues to be a controversial biomarker for both HAND and AD (Gisslen et al., EBioMedicine 3: 135-140, 2016; Kovacs et al., Eur J Neurol 24:1326-e77, 2017; Norgren et al., Brain Res 987: 25-31, 2003; Rolstad et al., J Alzheimers Dis 45: 873-881, 2015; Yilmaz et al., Expert Rev Mol Diagn 17: 761-770, 2017).
There was a stepwise increase in CSF NFL levels between control participants (median [range] score, 536 [398-777] pg/mL), participants with MCI (831 [526-1075] pg/mL), and those with Alzheimer disease (951 [758-1261] pg/mL), indicating that NFL levels increase with increasing cognitive impairment.
First, in a subsample of A+ AD dementia and matched biomarker-negative (i.e., A- and tau tangle pathology (T)-) CU controls (n = 40), we examined ROC characteristics and identified N cut-offs using Youden's J for neurofilament light chain protein (NfL) and each of three MRI-based measures: a thickness-based AD signature from FreeSurfer, hippocampal volume (using FIRST), and a simple estimate of global atrophy (the ratio of intracranial CSF segmented volume to brain tissue volume, using SPM12).
While there is variability in change over time, both within and between individuals, and more work is needed to understand the sources of this variability, serum NfL remains a promising, accessible biomarker of early neurodegeneration in presymptomatic Alzheimer's disease.
Neurofilament light chain (NfL), a marker of axonal degeneration, is robustly elevated in the blood of many neurological and neurodegenerative conditions, including AD.
We evaluated CSF amyloid-β (Aβ)42 and Aβ40, total (t)-tau, phosphorylated (p)-tau, total prion protein (t-PrP), and neurofilament light chain protein (NfL) in healthy controls (n = 50) and subjects with iNPH (n = 71), Alzheimer's disease (AD) (n = 60), and several other subtypes of dementia (n = 145).
545 eligible non-Hispanic white participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with longitudinal plasma NFL data were included.
An interaction also emerged for the Alzheimer's disease biomarker profiles (p = 0.046) where in comparison to the referent 'normal' biomarker group, individuals with abnormal levels of both Aβ42 and total tau showed stronger associations between vascular risk and neurofilament light.
Results from recent clinical studies suggest that cerebrospinal fluid (CSF) biomarkers that are indicative of Alzheimer's disease (AD) can be replicated in blood, e.g. amyloid-beta peptides (Aβ<sub>42</sub> and Aβ<sub>40</sub>) and neurofilament light chain (NFL).
Novel biomarkers (e.g., neurofilament light), new outcomes (e.g., AD Composite Score [ADCOMS]), enrollment of earlier populations, and innovative trial designs (e.g., Bayesian adaptive designs) are new features in recent clinical trials.
Despite p-tau/Aβ<sub>42</sub> and Aβ<sub>42</sub>/Aβ<sub>40</sub> levels comparable to those of the AD-Dementia group, mismatches had significantly lower levels of NFL and total tau.