title: Association of Plasma Neurofilament Light With Neurodegeneration in Patients With Alzheimer Disease.
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.
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden2Memory Clinic, Skåne University Hospital, Scania, Sweden3Department of Neurology, Skåne University Hospital, Scania, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Mattsson
authors.affiliation: Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden5Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Möndal, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Andreasson
authors.affiliation: Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden5Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Möndal, Sweden6Department of Molecular Neuroscience, University College London Institute of Neurology, Queen Square, London, England.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden5Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Möndal, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000000981:diagnostic imaging* / Q000503:physiopathology; D001284:Atrophy / Q000000981:diagnostic imaging; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000097:blood* / Q000000981:diagnostic imaging* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000097:blood*; D012042:Registries
chemical_list: D015415:Biomarkers; D016900:Neurofilament Proteins; C044882:neurofilament protein L