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Weiss, Alison R; Bertoglio, Daniele; Liguore, William A; Brandon, Kristin; Templon, John; Link, Jeanne; McBride, Jodi L
Movement disorders, 01/2023, Volume: 38, Issue: 1Journal Article
Dopamine system dysfunction and altered glucose metabolism are implicated in Huntington's disease (HD), a neurological disease caused by mutant huntingtin (mHTT) expression. 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. Positron emission tomography (PET) imaging was performed using Ffallypride to quantify D /D receptor density and 2- Ffluoro-2-deoxy-d-glucose ( FFDG) to measure cerebral glucose utilization in these HD macaques. 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). FFallypride and FFDG 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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