Objective: We aimed to evaluate the role of astroglia activation in Parkinson’s disease (PD) using [11C]BU99008 PET, a novel radioligand with high specificity and selectivity for imidazoline 2 binding sites (I2BS).

Background: In PD, astroglia cells display α-synuclein-positive accumulations in the cytoplasm and may play a role in disease initiation and progression. The imidazoline 2 binding sites (I2BS) are expressed on activated astrocytes; therefore, by measuring I2BS levels we can indirectly evaluate astrogliosis in PD.

Method: Twenty-two patients with PD, 8 early and 14 moderate/advanced, and 14 healthy controls (HCs) underwent MRI and [11C]BU9908 PET corrected with arterial input function. Regional volume of distribution (VT) was calculated using the two-tissue compartment model with MIAKAT.

Results: In early PD, increased [11C]BU99008 VT was observed in frontal, temporal, parietal and occipital cortical regions (P<0.05), with the greatest increase in the brainstem (P=0.018), compared to HCs. In moderate/advanced PD, loss of [11C]BU99008 VT uptake was observed across frontal, temporal, parietal, occipital, insula cortices, and the caudate, putamen, thalamus and brainstem (P<0.05). Loss of [11C]BU99008 VT in frontal (r=-0.61), temporal (r=-0.61), parietal (r=-0.59), occipital (r=0.58), insula (r=-0.60) cortices, and the caudate (r=-0.63), putamen (r=-0.620), thalamus (r=-0.61) and brainstem (r=-0.56) correlated with longer disease duration (P<0.05). In the subgroup of moderate/advanced Parkinson’s patients, loss of [11C]BU99008 VT in the frontal (r=0.78), temporal (r=0.735) and parietal (r=0.79) cortex correlated with global cognitive impairment (P<0.05).

Conclusion: This study demonstrates in vivo the role of astroglia in the initiation and progression of Parkinson’s disease. Astrogliosis observed early in Parkinson’s disease could reflect a neuroprotective compensatory mechanisms and pro-inflammatory upregulation in response to α-synuclein accumulation. However, as the disease progresses and significant neurodegeneration occurs, astroglia lose their reactive function and such loss in the cortex has clinical relevance in the development of cognitive impairment.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/evaluation-of-imidazoline-2-binding-sites-reflecting-astroglia-pathology-in-parkinsons-disease-an-in-vivo-11cbu99008-pet-study/