To investigate structural and functional changes in microglia in different stages of HD.

Previous studies have shown that inflammatory mechanisms are intrinsically associated with neurodegeneration. However, the role of both central nervous system and peripheral inflammation in HD is still poorly understood.

12 patients with a genetic diagnosis of HD [6 manifest patients (50.8±11.5y;6F), 6 premanifest HD gene carriers (38.2±7.2y;4M/2F)], and 6 controls (43.3±8.8y;5F/1M) underwent a [11C]-ER176 PET scan and an MRI for anatomical localization. Segmentation of region of interest (ROIs) was performed and group differences in [11C]-ER176 binding (used to evaluate the extent of microglial activation) were assessed by the standardized uptake value ratio (SUVR), that is, the ratio of brain uptake in ROIs to that in the cerebellum. Blood samples were collected and monocytes were used to generate induced microglia-like  cells (iMG). In vitro evaluation of the dynamic functions of microglia included a phagocytosis assay.

Patients with manifest HD present increased microglia activation in basal ganglia structures that are known to be involved in HD pathophysiology. Premanifest HD gene carriers present SUVRs similar to controls, thus concluding that microglia activation occurs later in HD pathology. It is important to refine the understanding of the more specific immune/inflammatory mechanisms that are involved in HD. This will allow the development of new therapeutic interventions to halt the progression of HD.