title: Diagnostic accuracy of CSF Ab42 and florbetapir PET for Alzheimer's disease.
abstract: BACKGROUND
  Reduced cerebrospinal fluid (CSF) β-amyloid42 (Aβ42) and increased florbetapir positron emission tomography (PET) uptake reflects brain Aβ accumulation. These biomarkers are correlated with each other and altered in Alzheimer's disease (AD), but no study has directly compared their diagnostic performance.
  
  
  METHODS
  We examined healthy controls (CN, N = 169) versus AD dementia patients (N = 118), and stable (sMCI; no dementia, followed up for at least 2 years, N = 165) versus progressive MCI (pMCI; conversion to AD dementia, N = 59). All subjects had florbetapir PET (global and regional; temporal, frontal, parietal, and cingulate) and CSF Aβ42 measurements at baseline. We compared area under the curve (AUC), sensitivity, and specificity (testing a priori and optimized cutoffs). Clinical diagnosis was the reference standard.
  
  
  RESULTS
  CSF Aβ42 and (global or regional) PET florbetapir did not differ in AUC (CN vs. AD, CSF 84.4%; global PET 86.9%; difference [95% confidence interval] -6.7 to 1.5). CSF Aβ42 and global PET florbetapir did not differ in sensitivity, but PET had greater specificity than CSF in most comparisons. Sixteen CN progressed to MCI and AD (six Aβ negative, seven Aβ positive, and three PET positive but CSF negative).
  
  
  CONCLUSIONS
  The overall diagnostic accuracies of CSF Aβ42 and PET florbetapir were similar, but PET had greater specificity. This was because some CN and sMCI subjects appear pathological using CSF but not using PET, suggesting that low CSF Aβ42 not always translates to cognitive decline or brain Aβ accumulation. Other factors, including costs and side effects, may also be considered when determining the optimal modality for different applications.
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg Mölndal, Sweden ; Department of Radiology and Biomedical Imaging, University of California San Francisco, California ; Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases San Francisco, California.
authors.forename: Niklas
authors.initials: N
authors.lastname: Mattsson
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California San Francisco, California.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Insel
authors.affiliation: Helen Wills Neuroscience Institute and School of Public Health, University of California Berkeley, California.
authors.forename: Susan
authors.initials: S
authors.lastname: Landau
authors.affiliation: Helen Wills Neuroscience Institute and School of Public Health, University of California Berkeley, California.
authors.forename: William
authors.initials: W
authors.lastname: Jagust
authors.affiliation: Division of Biostatistics and Bioinformatics, Department of Family & Preventive Medicine, University of California, San Diego La Jolla, California.
authors.forename: Michael
authors.initials: M
authors.lastname: Donohue
authors.affiliation: Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine Philadelphia, Pennsylvania.
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.affiliation: Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine Philadelphia, Pennsylvania.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg Mölndal, Sweden ; UCL Institute of Neurology Queen Square, London, WC1N 3BG, United Kingdom.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg Mölndal, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California San Francisco, California ; Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases San Francisco, California.
authors.forename: Michael
authors.initials: M
authors.lastname: Weiner