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In vivo microglia activation in very early dementia with Lewy bodies, comparison with Parkinson's disease
S Iannaccone1, C Cerami, M Alessio
1Neurorehabilitation Unit, Department of Clinical Neurosciences, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy.
Background:
Reactive microgliosis, hallmark of neuroinflammation, may contribute to neuronal degeneration, as shown in several neurodegenerative diseases. We in vivo evaluated microglia activation in early dementia with Lewy bodies, still not reported, and compared with early Parkinson's disease, to assess possible differential pathological patterns.
Methods:
We measured the [(11)C]-PK11195 binding potentials with Positron Emission Tomography, using a simplified reference tissue model, as marker of microglia activation, and cerebral spinal fluid protein carbonylation levels, as marker of oxidative stress. Six dementia with Lewy bodies and 6 Parkinson's disease patients within a year from the onset, and eleven healthy controls were included. Clinical diagnosis was confirmed at a 4-year follow-up.
Results:
In dementia with Lewy bodies as well as in Parkinson's disease, we found significant (p < 0.001) [(11)C]-PK11195 binding potential increases in the substantia nigra and putamen. Patients with Lewy bodies dementia had extensive additional microglia activation in several associative cortices. This was evident also at a single subject level. Significant increase of Cerebral Spinal Fluid protein carbonylation was shown in both patients' groups.
Conclusions:
[(11)C]-PK11195 Positron Emission Tomography imaging revealed neuroinflammation in dementia with Lewy bodies and Parkinson's disease, mirroring, even at a single subject level, the common and the different topographical distribution of neuropathological changes, yet in the earliest stages of the disease process. Focusing on those events that characterize parkinsonisms and Parkinson's disease may be the key to further advancing the understanding of pathogenesis and to taking these mechanisms forward as a means of defining targets for neuroprotection.
Insights
Neuroinflammation, marked by microglia activation, is present in early dementia with Lewy bodies and Parkinson's disease. Positron Emission Tomography imaging revealed distinct patterns of this inflammation, offering insights into disease progression.
Area of Science:
- Neuroscience
- Neurology
- Radiology
Background:
- Reactive microgliosis is a key feature of neuroinflammation and implicated in neurodegenerative diseases.
- Microglia activation in early dementia with Lewy bodies (DLB) has not been previously reported.
- This study aimed to compare in vivo microglia activation patterns in early DLB and early Parkinson's disease (PD).
Purpose of the Study:
- To evaluate and compare microglia activation in early DLB and early PD using in vivo imaging.
- To assess potential differential pathological patterns of neuroinflammation between DLB and PD.
- To investigate oxidative stress markers in relation to neuroinflammation in these early-stage neurodegenerative conditions.
Main Methods:
- Utilized [(11)C]-PK11195 Positron Emission Tomography (PET) to measure microglia activation.
- Employed a simplified reference tissue model for [(11)C]-PK11195 binding potential quantification.
- Measured cerebral spinal fluid (CSF) protein carbonylation as a marker of oxidative stress in 6 DLB patients, 6 PD patients, and 11 healthy controls.
Main Results:
- Significant [(11)C]-PK11195 binding increases were observed in the substantia nigra and putamen in both DLB and PD patients.
- DLB patients exhibited widespread additional microglia activation in associative cortices, evident even at the individual subject level.
- Elevated CSF protein carbonylation levels were found in both patient groups, indicating systemic oxidative stress.
Conclusions:
- [(11)C]-PK11195 PET imaging successfully visualized neuroinflammation in early DLB and PD.
- The imaging revealed common and distinct topographical distributions of neuropathological changes, mirroring early disease stages.
- Understanding these neuroinflammatory events is crucial for advancing the comprehension of parkinsonian pathogenesis and identifying neuroprotective targets.
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