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E01 Widespread loss of presynaptic terminal marker SV2A in early huntington disease
  1. Aline Delva1,2,
  2. Laura Michiels1,2,
  3. Michel Koole2,
  4. Koen Van Laere1,2,
  5. Wim Vandenberghe1,2
  1. 1University Hospitals Leuven, Leuven, Belgium
  2. 2KU Leuven, Leuven, Belgium

Abstract

Background Synaptic damage has long been suspected to play a major role in the pathophysiology of Huntington disease (HD), but in vivo evidence in humans is limited.

Aim To assess synaptic damage in early stages of HD in vivo.

Methods Eighteen HD mutation carriers (7 premanifest, 11 early manifest; 51.4±11.6 years; 6 female) and 15 age- and gender-matched healthy controls (52.3±3.5 years; 4 female) were included. Subjects underwent clinical assessment of motor and non-motor manifestations, MRI, PET with 11C-UCB-J, a radioligand targeting the ubiquitous presynaptic terminal marker SV2A, and 18F-FDG PET. Standardized uptake value ratio -1 images were calculated for 11C-UCB-J with the centrum semiovale as reference region. 18F-FDG PET activity was normalized to the pons. All PET data were corrected for partial volume effects.

Results 11C-UCB-J PET showed loss of SV2A binding in the HD group in putamen (-28%, p < 0.001), caudate (-25%, p < 0.001), pallidum (-24%, p < 0.001), cerebellum (-11%,p = 0.002), parietal (-9%, p = 0.004) and frontal cortex (-8%, p = 0.002). By contrast, 18F-FDG PET only showed significantly lower uptake in caudate (-31%) and putamen (-31%) (both p < 0.001). In the premanifest subgroup, 11C-UCB-J PET and 18F-FDG PET showed significant reductions in putamen and caudate only. In the HD group, 11C-UCB-J binding in caudate correlated with UHDRS motor score (r = -0.70, p = 0.001), SDMT (r = 0.67, p = 0.002) and AVLT sum (r = 0.69, p = 0.002), and 11C-UCB-J binding in putamen correlated with UHDRS motor score (r = -0.82, p < 0.001) and SDMT (r = 0.69, p = 0.001).

Conclusion 11C-UCB-J PET revealed extensive loss of SV2A in early HD, suggesting widespread synaptic disconnection. SV2A loss in the striatum correlated with motor and cognitive functioning. 11C-UCB-J PET is more sensitive than 18F-FDG PET for detection of extrAstriatal changes in early HD.

  • PET
  • UCB-J
  • synaptic
  • FDG

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