Association of Plasma Neurofilament Light With Neurodegeneration in Patients With Alzheimer Disease

TLDR

Current Alzheimer disease biomarkers such as CSF and tau PET are invasive or costly, so a blood‑based marker like plasma neurofilament light (NFL) has been proposed as a more accessible alternative. The study aimed to determine whether plasma NFL levels are elevated in AD and whether they correlate with cognitive decline, other AD biomarkers, and neurodegeneration imaging. Using an ultrasensitive assay, plasma NFL was measured in 193 controls, 197 MCI, and 180 AD patients in a prospective case‑control study (2005‑2012) with analysis in 2016, assessing associations with diagnosis, amyloid pathology, CSF injury markers, cognition, brain structure, and metabolism. Plasma NFL was higher in MCI and AD patients than controls, achieved an AUC of 0.87 for AD versus controls, was especially elevated in amyloid‑positive cases, and correlated with poorer cognition, AD‑related atrophy, and hypometabolism, supporting its potential as a noninvasive AD biomarker.

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.