Reduced D /D Receptor Binding and Glucose Metabolism in a Macaque Model of Huntington's Disease.
Alison R Weiss, Daniele Bertoglio, William A Liguore, Kristin Brandon, John Templon, Jeanne Link, Jodi L McBride
Author Information
- Alison R Weiss: Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon, USA. ORCID
- Daniele Bertoglio: Molecular Imaging Center Antwerp (MICA), University of Antwerp, Antwerp, Belgium. ORCID
- William A Liguore: Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon, USA.
- Kristin Brandon: Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon, USA.
- John Templon: Division of Cardiometabolic Health, Oregon National Primate Research Center, Beaverton, Oregon, USA.
- Jeanne Link: Center for Radiochemistry Research, OHSU Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon, USA.
- Jodi L McBride: Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon, USA. ORCID
BACKGROUND: Dopamine system dysfunction and altered glucose metabolism are implicated in Huntington's disease (HD), a neurological disease caused by mutant huntingtin (mHTT) expression.
OBJECTIVE: The aim was to characterize alterations in cerebral dopamine D /D receptor density and glucose utilization in a newly developed AAV-mediated NHP model of HD that expresses mHTT throughout numerous brain regions.
METHODS: Positron emission tomography (PET) imaging was performed using [ F]fallypride to quantify D /D receptor density and 2-[ F]fluoro-2-deoxy-d-glucose ([ F]FDG) to measure cerebral glucose utilization in these HD macaques.
RESULTS: Compared to controls, HD macaques showed significantly reduced dopamine D /D receptor densities in basal ganglia (P < 0.05). In addition, HD macaques displayed significant glucose hypometabolism throughout the cortico-basal ganglia network (P < 0.05).
CONCLUSIONS: [ F]Fallypride and [ F]FDG are PET imaging biomarkers of mHTT-mediated disease progression that can be used as noninvasive outcome measures in future therapeutic studies with this AAV-mediated HD macaque model. © 2022 International Parkinson and Movement Disorder Society.
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- P51 OD011092/NIH HHS
- F32 NS110149/NINDS NIH HHS
- R01 NS099136/NINDS NIH HHS
- T32 AG055378/NIA NIH HHS
- R01NS099136/NIH HHS
- T32AG055378/NIH HHS
- F32NS110149/NIH HHS
Animals
Fluorodeoxyglucose F18
Huntington Disease
Receptors, Dopamine D3
Dopamine
Macaca
Positron-Emission Tomography
Glucose
fallypride
Fluorodeoxyglucose F18
Receptors, Dopamine D3
Dopamine
Glucose
