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

Article type: Research Article

Authors: Gupta, Harsh V.^a | Beach, Thomas G.^b | Mehta, Shyamal H.^c | Shill, Holly A.^d | Driver-Dunckley, Erika^c | Sabbagh, Marwan N.^e | Belden, Christine M.^b | Liebsack, Carolyn^b | Dugger, Brittany N.^f | Serrano, Geidy E.^b | Sue, Lucia I.^b | Siderowf, Andrew^g | Pontecorvo, Michael J.^h | Mintun, Mark A.^h | Joshi, Abhinay D.^h | Adler, Charles H.^c

Affiliations: [a] Department of Neurology, The University of Kansas Health System, Kansas City, KS, USA | [b] Banner Sun Health Research Institute, Sun City, AZ, USA | [c] Department of Neurology, Mayo Clinic College of Medicine, Scottsdale, AZ, USA | [d] Barrow Neurological Institute, Phoenix, AZ, USA | [e] Ruvo Clinic, Las Vegas, NV, USA | [f] Department of Pathology and Laboratory Medicine, University of California-Davis School of Medicine, Sacramento, CA, USA | [g] Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA | [h] Avid Radiopharmaceuticals, Philadelphia, PA, USA

Correspondence: [*] Correspondence to: Harsh V. Gupta, MD, Assistant Professor of Neurology, The University of Kansas Health System, Kansas City, KS, USA. Tel.: +1 913 588 5000; E-mail: dr.harshgupta@gmail.com.

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: Alzheimer’s disease, amyloid, AV-133, dementia with Lewy bodies, synucleinopathy, VMAT2

DOI: 10.3233/JAD-200323

Journal: Journal of Alzheimer's Disease, vol. 80, no. 4, pp. 1603-1612, 2021