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Weiss, Alison R.; Bertoglio, Daniele; Liguore, William A.; Brandon, Kristin; Templon, John; Link, Jeanne; McBride, Jodi L.
Movement disorders, January 2023, Volume: 38, Issue: 1Journal Article
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 18Ffallypride to quantify D2/D3 receptor density and 2‐18Ffluoro‐2‐deoxy‐d‐glucose (18FFDG) 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 18FFallypride and 18FFDG 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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