Concordance between cerebrospinal fluid biomarkers and [11C]PIB PET in a memory clinic cohort

J Alzheimers Dis. 2014;41(3):801-7. doi: 10.3233/JAD-132561.

Abstract

Background: Two approaches are available for measuring Alzheimer's disease (AD) pathology in vivo. Biomarkers in cerebrospinal fluid (CSF) include amyloid-β1-42 (Aβ42) and tau. Furthermore, amyloid deposition can be visualized using positron emission tomography (PET) and [11C]Pittsburgh compound-B ([11C]PIB).

Objective: We investigated concordance between CSF biomarkers and [11C]PIB PET as markers for AD pathology in a memory clinic cohort.

Methods: We included 64 AD patients, 34 non-AD dementia patients, 22 patients with mild cognitive impairment (MCI), and 16 controls. [11C]PIB scans were visually rated as positive or negative. CSF biomarkers were considered abnormal based on Aβ42 alone (<550 ng/L), a more lenient Aβ42 cut-off (<640 ng/L) or a combination of both Aβ42 and tau ((373 + 0.82 tau)/Aβ42 > 1). Concordance between CSF biomarkers and [11C]PIB PET was determined.

Results: Overall, concordance between [11C]PIB PET and CSF Aβ42 (<550 ng/L) was 84%. In discordant cases, [11C]PIB PET was more often AD-positive than Aβ42. When a more lenient Aβ42 cut-point (<640 ng/L) or a combination of Aβ42 and tau was used, concordance with [11C]PIB PET appeared to be even higher (90% and 89%). This difference is explained by a subgroup of mostly MCI and AD patients with Aβ42 levels just above cut-off. Now, in discordant cases, CSF was more often AD-positive than [11C]PIB PET.

Conclusion: Concordance between CSF Aβ42 and [11C]PIB PET was good in all diagnostic groups. Discordance was mostly seen in MCI and AD patients close to the cut-point. These results provide convergent validity for the use of both types of biomarkers as measures of AD pathology.

Keywords: Alzheimer's disease; amyloid; cerebrospinal fluid; positron-emission tomography; tau.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease* / cerebrospinal fluid
  • Alzheimer Disease* / complications
  • Alzheimer Disease* / diagnostic imaging
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Aniline Compounds
  • Benzothiazoles*
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Memory Disorders* / cerebrospinal fluid
  • Memory Disorders* / diagnostic imaging
  • Memory Disorders* / etiology
  • Middle Aged
  • Neuropsychological Tests
  • Peptide Fragments / cerebrospinal fluid*
  • Positron-Emission Tomography
  • Psychiatric Status Rating Scales
  • Thiazoles
  • tau Proteins / cerebrospinal fluid*

Substances

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