Abstract
Existing cerebrospinal fluid (CSF) or imaging (tau positron emission tomography) biomarkers for Alzheimer disease (AD) are invasive or expensive. Biomarkers based on standard blood test results would be useful in research, drug development, and clinical practice. Plasma neurofilament light (NFL) has recently been proposed as a blood-based biomarker for neurodegeneration in dementias. To test whether plasma NFL concentrations are increased in AD and associated with cognitive decline, other AD biomarkers, and imaging evidence of neurodegeneration. In this prospective case-control study, an ultrasensitive assay was used to measure plasma NFL concentration in 193 cognitively healthy controls, 197 patients with mild cognitive impairment (MCI), and 180 patients with AD dementia from the Alzheimer's Disease Neuroimaging Initiative. The study dates were September 7, 2005, to February 13, 2012. The plasma NFL analysis was performed in September 2016. Associations were tested between plasma NFL and diagnosis, Aβ pathologic features, CSF biomarkers of neuronal injury, cognition, brain structure, and metabolism. Among 193 cognitively healthy controls, 197 patients with mild cognitive impairment, and 180 patients with AD with dementia, plasma NFL correlated with CSF NFL (Spearman ρ = 0.59, P < .001). Plasma NFL was increased in patients with MCI (mean, 42.8 ng/L) and patients with AD dementia (mean, 51.0 ng/L) compared with controls (mean, 34.7 ng/L) (P < .001) and had high diagnostic accuracy for patients with AD with dementia vs controls (area under the receiver operating characteristic curve, 0.87, which is comparable to established CSF biomarkers). Plasma NFL was particularly high in patients with MCI and patients with AD dementia with Aβ pathologic features. High plasma NFL correlated with poor cognition and AD-related atrophy (at baseline and longitudinally) and with brain hypometabolism (longitudinally). Plasma NFL is associated with AD diagnosis and with cognitive, biochemical, and imaging hallmarks of the disease. This finding implies a potential usefulness for plasma NFL as a noninvasive biomarker in AD.
Highlights
Plasma neurofilament light (NFL) was increased in patients with mild cognitive impairment (MCI) and patients with Alzheimer disease (AD) dementia compared with controls (P < .001) and had high diagnostic accuracy for patients with AD with dementia vs controls
Our group has recently transferred the cerebrospinal fluid (CSF) NFL assay to an ultrasensitive single-molecule array (Simoa; Quanterix Corporation) platform, which provides an analytical sensitivity of 0.6 pg/mL compared with 78.0 pg/mL for the corresponding enzyme-linked immunosorbent assay (ELISA).[10]
We tested the hypotheses that the plasma NFL concentration is increased in AD and that it correlates with impaired cognition, neuroimaging abnormalities, and CSF biomarkers of AD pathologic features
Summary
ADNI Study Design Data were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). The ADNI was launched in 2003 as a public-private partnership, led by principal investigator Michael W. MD (the most recent information on the ADNI is available at http://www .adni-info.org). The ADNI participants have been recruited from more than 50 sites across the United States and Canada. We used data accessed from the Laboratory of Neuro Imaging (University of Southern California) ADNI database on October 6, 2016. The study data and samples were collected from September 7, 2005, to February 13, 2012. Regional ethical committees of all participating institutions approved the ADNI. All study participants provided written informed consent
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