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Case Reports
. 2021;80(4):1603-1612.
doi: 10.3233/JAD-200323.

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

Harsh V Gupta  1 , Thomas G Beach  2 , Shyamal H Mehta  3 , Holly A Shill  4 , Erika Driver-Dunckley  3 , Marwan N Sabbagh  5 , Christine M Belden  2 , Carolyn Liebsack  2 , Brittany N Dugger  6 , Geidy E Serrano  2 , Lucia I Sue  2 , Andrew Siderowf  7 , Michael J Pontecorvo  8 , Mark A Mintun  8 , Abhinay D Joshi  8 , Charles H Adler  3
Affiliations
Case Reports

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

Harsh V Gupta et al. J Alzheimers Dis. 2021.

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.

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Figures

Fig. 1.
Fig. 1.
AV-133 PET images for the three studied cases. Case 1 (top) was read as having bilateral dopaminergic depletion in putamen and caudate by all 5 study readers. Case 2 (middle) was read as normal, without dopaminergic depletion in caudate or putamen, by all 5 readers. Case 3 (bottom) was read by all 5 readers as having a decreased signal in the left putamen, while 3/5 noted a decrease in right putamen and one indicated the decreases were asymmetrical, left > right; all 5 readers reported no decrease in left or right caudate nuclei.
Fig. 2.
Fig. 2.
Sections stained with an immunohistochemical method for VMAT2, showing the left anterior caudate nucleus from the three AV-133-imaged subjects (A, C, E) and three control subjects (B, D, F) without clinical dementia or parkinsonism. Scale bar (F) is 50 μm and serves for A–F.
Fig. 3.
Fig. 3.
Quantification of staining intensity in caudate nucleus sections stained with an immunohistochemical method for VMAT2, for the three AV-133-imaged subjects and three control subjects (B, D, F) without clinical dementia or parkinsonism.
See this image and copyright information in PMC

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