@article{2e6d3049237b46eca6520a30d9afccb2,
title = "Reduced D2/D3 Receptor Binding and Glucose Metabolism in a Macaque Model of Huntington's Disease",
abstract = "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 D2/D3 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 [18F]fallypride to quantify D2/D3 receptor density and 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) to measure cerebral glucose utilization in these HD macaques. Results: Compared to controls, HD macaques showed significantly reduced dopamine D2/D3 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: [18F]Fallypride and [18F]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.",
keywords = "2-[F]fluoro-2-deoxy-d-glucose, binding potential, cortical-basal ganglia, fallypride, positron emission tomography imaging",
author = "Weiss, {Alison R.} and Daniele Bertoglio and Liguore, {William A.} and Kristin Brandon and John Templon and Jeanne Link and McBride, {Jodi L.}",
note = "Funding Information: K.B. Stock ownership in medically related fields: none Intellectual property rights: none Consultancies: none Expert testimony: none Advisory boards: none Employment: full‐time employment at Rice University as a graduate student (K.B. performed all work on this grant while a research assistant in Dr. McBride's lab at the ONPRC before enrolling in graduate school) Partnerships: none Contracts: none Honoraria: none Royalties: none Grants: Dean of Natural Sciences Worden Fellowship, Dean of Graduate Studies First Year Fellowship Other: none Funding Information: W.A.L. Stock ownership in medically related fields: none Intellectual property rights: none Consultancies: none Expert testimony: none Advisory boards: none Employment: full‐time employment as senior research assistant at the Oregon National Primate Research Center Partnerships: none Contracts: none Honoraria: none Royalties: none Grants: supported by NIH grants NS099136, U01 NS116752, Bev Hartig HD Foundation, CHDI Foundation, and Noah's Hope Foundation Other: none Funding Information: J.L.M. Stock ownership in medically related fields: none Intellectual property rights: none Consultancies: Sanofi, Voyager Therapeutics, and Capsigen (regarding gene therapy for neurodegenerative disorders) Expert testimony: none Advisory boards: none Employment: full‐time employment as associate professor at the Oregon National Primate Research Center Partnerships: none Contracts: none Honoraria: honoraria for delivering seminars to Voyager Therapeutics and Sanford Research Royalties: none Grants: supported by NIH grants NS099136, U01 NS116752, Bev Hartig HD Foundation, CHDI Foundation, and Noah's Hope Foundation Other: none Funding Information: We express our gratitude to the ONPRC Division of Animal Resources and Research Support for the excellent care provided to the animals involved in this study, with special acknowledgment to the expert veterinary efforts that Drs. Lauren Drew Martin and Theodore Hobbs contributed to this work. D.B. is a member of the μNeuro Research Centre of Excellence at the University of Antwerp. Publisher Copyright: {\textcopyright} 2022 International Parkinson and Movement Disorder Society.",
year = "2023",
month = jan,
doi = "10.1002/mds.29271",
language = "English (US)",
volume = "38",
pages = "143--147",
journal = "Movement Disorders",
issn = "0885-3185",
publisher = "John Wiley and Sons Inc.",
number = "1",
}