Microglial activation correlates with severity in Huntington disease

Abstract

These [(11)C](R)-PK11195 PET findings show that the level of microglial activation correlates with Huntington disease (HD) severity. They lend support to the view that microglia contribute to the ongoing neuronal degeneration in HD and indicate that [(11)C](R)-PK11195 PET provides a valuable marker when monitoring the efficacy of putative neuroprotecting agents in this relentlessly progressive genetic disorder.

Positron Emission Tomography Imaging of Neuroinflammation

“…51 In vivo evidence of increased [ 11 C](R)-PK11195 binding in the striatum and cortical regions in symptomatic HD patients compared with healthy controls has been recently published. 52 In that study, [ 11 C](R)-PK11195 binding correlated with clinical severity of HD rated with Unified HD Rating Scale motor scores, and inversely with the level of striatal dopamine D2 receptor loss as assessed by [ 11 C]raclopride PET. The authors also reported that increased striatal [ 11 C](R)-PK11195 binding was present in a few presymptomatic HD gene carriers.…”

Chemokine Interleukin-8 (IL-8) in Alzheimer’s and Other Neurodegenerative Diseases

“…Microglial activation also demonstrated both temporal and spatial correlations with neuronal damage and dysfunction. Importantly, microglial activation and brain inflammation was associated with the severity in the progression of the disease [18]. Increased levels of IL-8 have been reported in HD brain [19] and in post-mortem samples from HD patients [20].…”

Imaging of neuroinflammation

“…Increased brain binding of 11 C-PK11195 was observed in several acute neurological and neurodegenerative disorders such as strokeinduced brain injury, multiple sclerosis, glioma, refractory epilepsy, AD and HD [8][9][10][11][12][13]. Increased uptake of 11 C-PK11195 was also reported in frontotemporal lobar degeneration [14] and HD [15]. In preclinical HD, regional brain atrophy and increased levels of microglial activation in the associative striatum areas (AST) correlated with HD onset [13].…”