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


Journal

Journal of Alzheimer's disease : JAD
ISSN: 1875-8908
Titre abrégé: J Alzheimers Dis
Pays: Netherlands
ID NLM: 9814863

Informations de publication

Date de publication:
2021
Historique:
pubmed: 16 3 2021
medline: 18 9 2021
entrez: 15 3 2021
Statut: ppublish

Résumé

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. 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). 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. 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 33720879
pii: JAD200323
doi: 10.3233/JAD-200323
pmc: PMC10109539
mid: NIHMS1886177
doi:

Substances chimiques

Amyloid 0
Aniline Compounds 0
Ethylene Glycols 0
Fluorine Radioisotopes 0
Radiopharmaceuticals 0
florbetapir 6867Q6IKOD
florbenazine F 18 KM31LBX59H
Dopamine VTD58H1Z2X
Tetrabenazine Z9O08YRN8O

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1603-1612

Subventions

Organisme : NIA NIH HHS
ID : P30 AG019610
Pays : United States
Organisme : NINDS NIH HHS
ID : U24 NS072026
Pays : United States

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Auteurs

Harsh V Gupta (HV)

Department of Neurology, The University of Kansas Health System, Kansas City, KS, USA.

Thomas G Beach (TG)

Banner Sun Health Research Institute, Sun City, AZ, USA.

Shyamal H Mehta (SH)

Department of Neurology, Mayo Clinic College of Medicine, Scottsdale, AZ, USA.

Holly A Shill (HA)

Barrow Neurological Institute, Phoenix, AZ, USA.

Erika Driver-Dunckley (E)

Department of Neurology, Mayo Clinic College of Medicine, Scottsdale, AZ, USA.

Marwan N Sabbagh (MN)

Ruvo Clinic, Las Vegas, NV, USA.

Christine M Belden (CM)

Banner Sun Health Research Institute, Sun City, AZ, USA.

Carolyn Liebsack (C)

Banner Sun Health Research Institute, Sun City, AZ, USA.

Brittany N Dugger (BN)

Department of Pathology and Laboratory Medicine, University of California-Davis School of Medicine, Sacramento, CA, USA.

Geidy E Serrano (GE)

Banner Sun Health Research Institute, Sun City, AZ, USA.

Lucia I Sue (LI)

Banner Sun Health Research Institute, Sun City, AZ, USA.

Andrew Siderowf (A)

Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.

Michael J Pontecorvo (MJ)

Avid Radiopharmaceuticals, Philadelphia, PA, USA.

Mark A Mintun (MA)

Avid Radiopharmaceuticals, Philadelphia, PA, USA.

Abhinay D Joshi (AD)

Avid Radiopharmaceuticals, Philadelphia, PA, USA.

Charles H Adler (CH)

Department of Neurology, Mayo Clinic College of Medicine, Scottsdale, AZ, USA.

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Classifications MeSH