Concordance and Diagnostic Accuracy of [11C]PIB PET and Cerebrospinal Fluid Biomarkers in a Sample of Patients with Mild Cognitive Impairment and Alzheimer's Disease

J Alzheimers Dis. 2015;45(4):1077-88. doi: 10.3233/JAD-142952.


Background: Alzheimer's disease (AD) pathology can be quantified in vivo using cerebrospinal fluid (CSF) levels of amyloid-β1-42 (Aβ1-42), total-tau (t-tau), and phosphorylated tau (p-tau181p), as well as with positron emission tomography (PET) using [(11)C]Pittsburgh compound-B ([(11)C]PIB). Studies assessing concordance between these measures, however, have provided conflicting results. Moreover, it has been proposed that [(11)C]PIB PET may be of greater clinical utility in terms of identifying patients with mild cognitive impairment (MCI) who will progress to the dementia phase of AD.

Objective: To determine concordance and classification accuracy of CSF biomarkers and [(11)C]PIB PET in a cohort of patients with MCI and AD.

Methods: 68 patients (MCI, n = 33; AD, n = 35) underwent [(11)C]PIB PET and CSF sampling. Cutoffs of >1.41 ([(11)C]PIB), <450 pg/mL-and a more lenient cutoff of 550 pg/mL-(Aβ1-42), <6.5 (Aβ1-42/p-tau181p), and 1.14 (Aβ1-42/t-tau), were used to determine concordance. Logistic regression was used to determine classification accuracy with respect to stable MCI (sMCI) versus MCI who progressed to AD (pMCI).

Results: Concordance between [(11)C]PIB and Aβ1-42 was highest for sMCI (67%), followed by AD (60%) and pMCI (33%). Agreement was increased across groups using Aβ1-42 <550 pg/mL, or Aβ1-42 to tau ratios. Logistic regression showed that classification accuracy of [(11)C]PIB, between sMCI and pMCI, was superior to Aβ1-42 (73% versus 58%), Aβ1-42/t-tau (63%), and Aβ1-42/p-tau181p (65%).

Conclusion: In the present study, [(11)C]PIB proved a better predictor of progression to AD in patients with MCI, relative to CSF measures of Aβ1-42 or Aβ1-42/tau. Discordance between PET and CSF markers for Aβ1-42 suggests they cannot be used interchangeably, as is currently the case.

Keywords: Alzheimer's disease; [${11}^C$]PIB; amyloid; cerebrospinal fluid; mild cognitive impairment; positron emission tomography; tau.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / classification
  • Alzheimer Disease / diagnostic imaging*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Aniline Compounds
  • Benzothiazoles
  • Biomarkers / cerebrospinal fluid
  • Brain / diagnostic imaging*
  • Cognitive Dysfunction / cerebrospinal fluid*
  • Cognitive Dysfunction / classification
  • Cognitive Dysfunction / diagnostic imaging*
  • Cohort Studies
  • Diagnosis, Differential
  • Female
  • Follow-Up Studies
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Peptide Fragments / cerebrospinal fluid
  • Phosphorylation
  • Positron-Emission Tomography
  • Radiopharmaceuticals
  • Thiazoles
  • tau Proteins / cerebrospinal fluid


  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Benzothiazoles
  • Biomarkers
  • MAPT protein, human
  • Peptide Fragments
  • Radiopharmaceuticals
  • Thiazoles
  • amyloid beta-protein (1-42)
  • tau Proteins