Amyloid tracers binding sites in autosomal dominant and sporadic Alzheimer's disease

Alzheimers Dement. 2017 Apr;13(4):419-430. doi: 10.1016/j.jalz.2016.08.006. Epub 2016 Sep 28.

Abstract

Introduction: Amyloid imaging has been integrated into diagnostic criteria for Alzheimer's disease (AD). How amyloid tracers binding differ for different tracer structures and amyloid-β aggregates in autosomal dominant AD (ADAD) and sporadic AD is unclear.

Methods: Binding properties of different amyloid tracers were examined in brain homogenates from six ADAD with APPswe, PS1 M146V, and PS1 EΔ9 mutations, 13 sporadic AD, and 14 control cases.

Results: 3H-PIB, 3H-florbetaben, 3H-AZD2184, and BTA-1 shared a high- and a varying low-affinity binding site in the frontal cortex of sporadic AD. AZD2184 detected another binding site (affinity 33 nM) in the frontal cortex of ADAD. The 3H-AZD2184 and 3H-PIB binding were significantly higher in the striatum of ADAD compared to sporadic AD and control. Polyphenol resveratrol showed strongest inhibition on 3H-AZD84 binding followed by 3H-florbetaben and minimal on 3H-PIB.

Discussion: This study implies amyloid tracers of different structures detect different sites on amyloid-β fibrils or conformations.

Keywords: AZD2184; Alzheimer's disease; Amyloid-β; Autosomal dominant Alzheimer's disease; Florbetaben; Pittsburgh compound B; Positron emission tomography; Resveratrol.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Binding, Competitive
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Brain / pathology
  • Central Nervous System Agents / chemistry
  • Central Nervous System Agents / pharmacokinetics*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Protein Binding
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics*

Substances

  • Amyloid beta-Peptides
  • Central Nervous System Agents
  • Radiopharmaceuticals