Clinicopathological Correlation: Dopamine and Amyloid PET Imaging with Neuropathology in Three Subjects Clinically Diagnosed with Alzheimer's Disease or Dementia with Lewy Bodies

J Alzheimers Dis. 2021;80(4):1603-1612. doi: 10.3233/JAD-200323.

Abstract

Background: Imaging biomarkers have the potential to distinguish between different brain pathologies based on the type of ligand used with PET. AV-45 PET (florbetapir, Amyvid™) is selective for the neuritic plaque amyloid of Alzheimer's disease (AD), while AV-133 PET (florbenazine) is selective for VMAT2, which is a dopaminergic marker.

Objective: To report the clinical, AV-133 PET, AV-45 PET, and neuropathological findings of three clinically diagnosed dementia patients who were part of the Avid Radiopharmaceuticals AV133-B03 study as well as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND).

Methods: Three subjects who had PET imaging with both AV-133 and AV-45 as well as a standardized neuropathological assessment were included. The final clinical, PET scan, and neuropathological diagnoses were compared.

Results: The clinical and neuropathological diagnoses were made blinded to PET scan results. The first subject had a clinical diagnosis of dementia with Lewy bodies (DLB); AV-133 PET showed bilateral striatal dopaminergic degeneration, and AV-45 PET was positive for amyloid. The final clinicopathological diagnosis was DLB and AD. The second subject was diagnosed clinically with probable AD; AV-45 PET was positive for amyloid, while striatal AV-133 PET was normal. The final clinicopathological diagnosis was DLB and AD. The third subject had a clinical diagnosis of DLB. Her AV-45 PET was positive for amyloid and striatal AV-133 showed dopaminergic degeneration. The final clinicopathological diagnosis was multiple system atrophy and AD.

Conclusion: PET imaging using AV-133 for the assessment of striatal VMAT2 density may help distinguish between AD and DLB. However, some cases of DLB with less-pronounced nigrostriatal dopaminergic neuronal loss may be missed.

Keywords: AV-133; Alzheimer’s disease; VMAT2; amyloid; dementia with Lewy bodies; synucleinopathy.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / pathology
  • Amyloid / metabolism*
  • Aniline Compounds / adverse effects
  • Dopamine / metabolism*
  • Ethylene Glycols / adverse effects
  • Fatal Outcome
  • Female
  • Fluorine Radioisotopes / adverse effects
  • Humans
  • Lewy Body Disease / diagnostic imaging*
  • Lewy Body Disease / pathology
  • Male
  • Middle Aged
  • Plaque, Amyloid / diagnostic imaging
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals
  • Tetrabenazine / adverse effects
  • Tetrabenazine / analogs & derivatives

Substances

  • Amyloid
  • Aniline Compounds
  • Ethylene Glycols
  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • florbetapir
  • florbenazine F 18
  • Dopamine
  • Tetrabenazine