Astrogliosis in aging and Parkinson's disease dementia: a new clinical study with C-11-BU99008 PET

Resumen:
This is an imaging study in Parkinson's disease dementia with C-11-BU99008 PET (experimental radioligand developed to assess astrocytic distribution in the living brain). Mohamed M. and Zeng Z et al. report that astrogliosis is common with aging in a region-specific manner. Here, C-11-BU99008 PET does not differentiate these patients from healthy controls. The role of astrogliosis in the pathology of brain aging and neurodegenerative diseases has recently drawn great attention. Imidazoline-2 binding sites represent a possible target to map the distribution of reactive astrocytes. In this study, we use C-11-BU99008, an imidazoline-2 binding sites-specific PET radioligand, to image reactive astrocytes in vivo in healthy controls and patients with established Parkinson's disease dementia. Eighteen healthy controls (age: 45-78 years) and six patients with Parkinson's disease dementia (age: 64-77 years) had one C-11-BU99008 PET-CT scan with arterial input function. All subjects underwent one 3 T MRI brain scan to facilitate the analysis of the PET data and to capture individual cerebral atrophy. Regional C-11-BU99008 volumes of distribution were calculated for each subject by the two-tissue compartmental modelling. Positive correlations between C-11-BU99008 volumes of distribution values and age were found for all tested regions across the brain within healthy controls (P < 0.05); furthermore, multiple regression indicated that aging affects C-11-BU99008 volumes of distribution values in a region-specific manner. Independent samples t-test indicated that there was no significant group difference in C-11-BU99008 volumes of distribution values between Parkinson's disease dementia (n = 6; mean age = 71.97 +/- 4.66 years) and older healthy controls (n = 9; mean age = 71.90 +/- 5.51 years). Our data set shows that astrogliosis is common with aging in a region-specific manner. However, in this set-up, C-11-BU99008 PET cannot differentiate patients with Parkinson's disease dementia from healthy controls of similar age.