Journal article
Association of Plasma Neurofilament Light With Neurodegeneration in Patients With Alzheimer Disease
JAMA neurology, Vol.74(5), pp.557-566
05/01/2017
DOI: 10.1001/jamaneurol.2016.6117
PMCID: PMC5822204
PMID: 28346578
Abstract
IMPORTANCE 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.
OBJECTIVE To test whether plasma NFL concentrations are increased in AD and associated with cognitive decline, other AD biomarkers, and imaging evidence of neurodegeneration.
DESIGN, SETTING, AND PARTICIPANTS 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.
MAIN OUTCOMES AND MEASURES Associationswere tested between plasma NFL and diagnosis, A beta pathologic features, CSF biomarkers of neuronal injury, cognition, brain structure, and metabolism.
RESULTS 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 rho = 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 A beta pathologic features. High plasma NFL correlated with poor cognition and AD-related atrophy (at baseline and longitudinally) and with brain hypometabolism (longitudinally).
CONCLUSIONS AND RELEVANCE 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.
Details
- Title: Subtitle
- Association of Plasma Neurofilament Light With Neurodegeneration in Patients With Alzheimer Disease
- Creators
- Niklas Mattsson - Lund UniversityUlf Andreasson - Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, SwedenHenrik Zetterberg - Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, SwedenKaj Blennow - Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, SwedenAlzheimer’s Disease Neuroimaging Initiative
- Contributors
- Hristina Koleva (Contributor) - University of Iowa, Psychiatry
- Resource Type
- Journal article
- Publication Details
- JAMA neurology, Vol.74(5), pp.557-566
- DOI
- 10.1001/jamaneurol.2016.6117
- PMID
- 28346578
- PMCID
- PMC5822204
- NLM abbreviation
- JAMA Neurol
- ISSN
- 2168-6149
- eISSN
- 2168-6157
- Publisher
- Amer Medical Assoc
- Number of pages
- 10
- Grant note
- Thelma Zoega Foundation Biotech BioClinica Inc Bristol-Myers Squibb Swedish Research Council; European Commission National Institute of Biomedical Imaging and Bioengineering; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Biomedical Imaging & Bioengineering (NIBIB) CereSpir Inc Eli Lilly and Company; Eli Lilly Cogstate; CogState Limited F. Hoffmann-La Roche Ltd and its affiliated company Genentech Inc; Hoffmann-La Roche Merck Co Inc; Merck & Company GE Healthcare; General Electric Lundbeck; Lundbeck Corporation AbbVie Meso Scale Diagnostics LLC EuroImmun U01 AG024904 / Alzheimer's Disease Neuroimaging Initiative (ADNI) from the National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA IXICO Ltd Lumosity Biogen Piramal Imaging Servier Canadian Institutes of Health Research; Canadian Institutes of Health Research (CIHR) Elan Pharmaceuticals Inc NeuroRx Research Takeda Pharmaceutical Company; Takeda Pharmaceutical Company Ltd W81XWH-12-2-0012 / Department of Defense OD ADNI; United States Department of Defense Johnson & Johnson Pharmaceutical Research & Development LLC; Johnson & Johnson; Johnson & Johnson USA Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's Disease) at Lund University European Research Council; European Research Council (ERC); European Commission Araclon Frimurarestiftelsen Alzheimer's Association Swedish State Support for Clinical Research Vinnova Janssen Alzheimer Immunotherapy Research & Development LLC Neurotrack Technologies Transition Therapeutics Fujirebio Europe National Institute on Aging; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) Alzheimer's Drug Discovery Foundation Novartis Pharmaceuticals Corporation; Novartis Pfizer Inc; Pfizer Greta and Johan Kock Foundation Swedish Alzheimer Foundation U01AG024904 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) Eisai Inc; Eisai Co Ltd
- Language
- English
- Date published
- 05/01/2017
- Academic Unit
- Psychiatry
- Record Identifier
- 9984293752602771
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