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Widespread microglial activation in multiple system atrophy.

ABSTRACT: BACKGROUND:The pattern and role of microglial activation in multiple system atrophy is largely unclear. The objective of this study was to use [11 C](R)-PK11195 PET to determine the extent and correlation of activated microglia with clinical parameters in MSA patients. METHODS:Fourteen patients with the parkinsonian phenotype of MSA (MSA-P) with a mean disease duration of 2.9 years (range 2-5 years) were examined with [11 C](R)-PK11195 PET and compared with 10 healthy controls. RESULTS:Patients with the parkinsonian phenotype of MSA showed a significant (P ? 0.01) mean increase in binding potentials compared with healthy controls in the caudate nucleus, putamen, pallidum, precentral gyrus, orbitofrontal cortex, presubgenual anterior cingulate cortex, and the superior parietal gyrus. No correlations between binding potentials and clinical parameters were found. CONCLUSIONS:In early clinical stages of the parkinsonian phenotype of MSA, there is widespread microglial activation as a marker of neuroinflammatory changes without correlation to clinical parameters in our patient population. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

SUBMITTER: Kubler D

PROVIDER: S-EPMC6659386 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Widespread microglial activation in multiple system atrophy.

Kübler Dorothee D Wächter Tobias T Cabanel Nicole N Su Zhangjie Z Turkheimer Federico E FE Dodel Richard R Brooks David J DJ Oertel Wolfgang H WH Gerhard Alexander A

Movement disorders : official journal of the Movement Disorder Society 20190206 4

<h4>Background</h4>The pattern and role of microglial activation in multiple system atrophy is largely unclear. The objective of this study was to use [<sup>11</sup> C](R)-PK11195 PET to determine the extent and correlation of activated microglia with clinical parameters in MSA patients.<h4>Methods</h4>Fourteen patients with the parkinsonian phenotype of MSA (MSA-P) with a mean disease duration of 2.9 years (range 2-5 years) were examined with [<sup>11</sup> C](R)-PK11195 PET and compared with 1 ...[more]

PMID: 30726574

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Project description:Multiple system atrophy (MSA) is an orphan, fatal, adult-onset neurodegenerative disorder of uncertain etiology that is clinically characterized by various combinations of parkinsonism, cerebellar, autonomic, and motor dysfunction. MSA is an ?-synucleinopathy with specific glioneuronal degeneration involving striatonigral, olivopontocerebellar, and autonomic nervous systems but also other parts of the central and peripheral nervous systems. The major clinical variants correlate with the morphologic phenotypes of striatonigral degeneration (MSA-P) and olivopontocerebellar atrophy (MSA-C). While our knowledge of the molecular pathogenesis of this devastating disease is still incomplete, updated consensus criteria and combined fluid and imaging biomarkers have increased its diagnostic accuracy. The neuropathologic hallmark of this unique proteinopathy is the deposition of aberrant ?-synuclein in both glia (mainly oligodendroglia) and neurons forming glial and neuronal cytoplasmic inclusions that cause cell dysfunction and demise. In addition, there is widespread demyelination, the pathogenesis of which is not fully understood. The pathogenesis of MSA is characterized by propagation of misfolded ?-synuclein from neurons to oligodendroglia and cell-to-cell spreading in a "prion-like" manner, oxidative stress, proteasomal and mitochondrial dysfunction, dysregulation of myelin lipids, decreased neurotrophic factors, neuroinflammation, and energy failure. The combination of these mechanisms finally results in a system-specific pattern of neurodegeneration and a multisystem involvement that are specific for MSA. Despite several pharmacological approaches in MSA models, addressing these pathogenic mechanisms, no effective neuroprotective nor disease-modifying therapeutic strategies are currently available. Multidisciplinary research to elucidate the genetic and molecular background of the deleterious cycle of noxious processes, to develop reliable biomarkers and targets for effective treatment of this hitherto incurable disorder is urgently needed.

Dataset Information

Widespread microglial activation in multiple system atrophy.

Publications

Widespread microglial activation in multiple system atrophy.

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