Tesi di specializzazione (5 anni)
Neuroinflammation and neurodegenerative diseases: a single subject analysis
MEDICINA CLINICA E SPERIMENTALE
Corso di studi
relatore Prof. Monzani, Fabio
correlatore Dott. Edison, Paul
correlatore Dott. Edison, Paul
Data inizio appello
Data di rilascio
Common causes of neurodegenerative dementia are Alzheimer’s disease (AD), vascular dementia, Parkinson’s disease dementia (PDD) and Frontotemporal dementia (FTD). Despite the different neuropathological features, neuroinflammation is a common process. Microglial cells play a significant role in these neurodegenerative process, leading to a vicious circle of self-sustaining inflammatory reaction between microglia, astrocytes and damaged neurons. Activated microglia express high levels of the 18-kDa mitochondrial translocator protein (TSPO); this could be imaged by (11)C-(R)-PK11195 PET (positron emission tomography) radioactive tracer, and is considered as a marker of neuroinflammation. Here we hypothesise that neuroinflammation is a diffuse and common process throughout the cortex in neurodegenerative diseases, but inhomogeneous in different cortical regions. Region on Interest (ROI) analysis might underestimate significant clusters across different predefined regions. To assess the amount of microglial activation in individual subjects, we introduced the single subject SPM analysis, by which we compared each subject from the disease group to the whole control group. We also created a 3D binding map to better visualize the cluster of inflammation. In this study we analyzed 37 patients (10 AD, 10 MCI, 11 PDD and 6 PD) and 8 controls. At ROI analysis, we detected significant PK11195 Binding Potential (BP) in almost all the region examined in AD and MCI patients, while PK11195 BP was also increased in PDD and PD subjects. Using single subject SPM analysis, we detected significant increase in [11C](R)PK11195 BP in frontal, temporal and parietal lobe in 7 out of 10 subjects; big clusters of occipital uptake can be detected in 5 out of 10 subject, but smaller uptake in the same region was seen in all the subjects in AD group. In MCI group, significant uptake in frontal, temporal and parietal lobe was detected in 6 out of 10 subjects. PD population was characterized by microglial uptake through out the cortex in 2 subjects, and uptake in occipital, temporal and parietal cortical regions in 3 subjects. The comparison between PDD group and controls showed whole brain PK11195 BP in the whole cortex in 3 patients; fronto-temporal and occipital uptake in other 3 subjects, mostly frontal uptake in other 2 subjects. In the other 3 patients smallest clusters of PK11195 BP can be seen in frontal, temporal and parietal cortex. We also found inverse correlation between MMSE and PK11195 BP in AD group. This study confirmed that neuroinflammation as a diffuse and common process in neurodegenerative diseases; and when present in neurodegenerative disease, it is throughout the cortex.
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