Plasma Neurofilament Light Predicts Alzheimer Neurodegeneration

By Will Boggs MD

NEW YORK (Reuters Health) - Longitudinal plasma neurofilament light (NfL) levels are associated with neurodegeneration in Alzheimer disease, researchers report.

"Plasma NfL is a noninvasive biomarker which may give information about the progressive neurodegeneration in patients with Alzheimer's disease," said Dr. Niklas Mattsson from Lund University, in Malmoe, Sweden.

"This biomarker is one of several novel blood based biomarkers for Alzheimer's disease and may in the future be used together with plasma measures of beta-amyloid and tau for a comprehensive work-up of Alzheimer's disease and other dementias," he told Reuters Health by email.

NfL is a sensitive biomarker for neuroaxonal damage whose levels correlate with future atrophy, hypometabolism and cognitive decline. But there are few studies of longitudinal plasma NfL levels in Alzheimer disease.

Dr. Mattsson's team used data from the Alzheimer Disease Neuroimaging Initiative (ADNI) database to evaluate longitudinal plasma NfL levels in 1,583 individuals, including 401 cognitively unimpaired controls, 855 with mild cognitive impairment (MCI) and 327 with Alzheimer dementia (AD).

At baseline, mean plasma NfL levels were higher in patients with MCI (37.9 ng/L) and AD (45.9 ng/L) than in controls (32.1 ng/L).

NfL increased significantly over time in all groups, with the greatest increases among patients with AD (4.9 ng/L/year vs. 2.7 ng/L/year among patients with MCI and 2.4 ng/L/year among controls), the researchers report in JAMA Neurology, online April 22.

Other biomarkers, imaging findings and cognitive measures were significantly associated with baseline NfL and with longitudinal changes in NfL levels.

Abeta42 was the CSF biomarker most strongly associated with longitudinal NfL levels. Hippocampal volume and entorhinal cortical thickness were the imaging measures with the strongest association with NfL slope, and ADAS-Cog score had the strongest association of the cognitive measures.

Variability of NfL slopes was highest in the AD group, in Abeta-positive participants and in participants classified as T+ in the Abeta, tau and neurodegeneration (ATN) classification scheme.

"I think there are several potential usages" of NfL, Dr. Mattsson said. "One may be as a noninvasive test in the work-up of cognitive impairment, where elevated plasma NfL levels may increase the likelihood that neurodegeneration is present. Another may be for longitudinal follow-up, to detect changes over time that indicate the presence of a pathological process. Finally, if a disease-modifying treatment becomes available, plasma NfL may be used as a tool to detect and monitor drug response."

Dr. Alberto Lleo Bisa from Hospital de la Santa Creu i Sant Pau, in Barcelona, Spain, who recently evaluated longitudinal CSF biomarker trajectories along the AD continuum, told Reuters Health by email that NfL "could have a role in clinical practice in the near future in the screening of patients with cognitive impairment as a surrogate marker of progression."

"Before this can be introduced in practice, it is important to investigate the generalizability of the NfL assay in other centers (how preanalytics influence the measure) and other cohorts (ADNI focuses only on AD spectrum) that better represent the patients seen in a Memory Unit (comorbidities, vascular component, etc.)," said Dr. Lleo, who was not involved in the study. "Whether this pattern is observed in other dementias (frontotemporal dementia, vascular dementia, Lewy body dementia, and so on) has to be clarified."

SOURCE: https://bit.ly/2GsJvYH

JAMA Neurol 2019.

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