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Microglia, amyloid, and glucose metabolism in Parkinson's disease with and without dementia.

Edison, Paul; Ahmed, Imtiaz; Fan, Zhen; Hinz, Rainer; Gelosa, Giorgio; Ray Chaudhuri, K; Walker, Zuzana; Turkheimer, Federico E; Brooks, David J

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2013;38(6):938-49.

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Abstract

[11C](R)PK11195-PET measures upregulation of translocator protein, which is associated with microglial activation, [11C]PIB-PET is a marker of amyloid, while [18F]FDG-PET measures cerebral glucose metabolism (rCMRGlc). We hypothesize that microglial activation is an early event in the Parkinson's disease (PD) spectrum and is independent of the amyloid pathology. The aim of this study is to evaluate in vivo the relationship between microglial activation, amyloid deposition, and glucose metabolism in Parkinson's disease dementia (PDD) and PD subjects without dementia. Here, we evaluated 11 PDD subjects, 8 PD subjects without dementia, and 24 control subjects. Subjects underwent T1 and T2 MRI, [11C](R)PK11195, [18F]FDG, and [11C]PIB PET scans. Parametric maps of [11C](R)PK11195 binding potential, rCMRGlc, and [11C]PIB uptake were interrogated using region of interest and SPM (statistical parametric mapping) analysis. The PDD patients showed a significant increase of microglial activation in anterior and posterior cingulate, striatum, frontal, temporal, parietal, and occipital cortical regions compared with the controls. The PD subjects also showed a statistically significant increase in microglial activation in temporal, parietal, and occipital regions. [11C]PIB uptake was marginally increased in PDD and PD. There was a significant reduction in glucose metabolism in PDD and PD. We have also demonstrated pixel-by-pixel correlation between mini-mental state examination (MMSE) score and microglial activation, and MMSE score and rCMRGlc. In conclusion, we have demonstrated that cortical microglial activation and reduced glucose metabolism can be detected early on in this disease spectrum. Significant microglial activation may be a factor in driving the disease process in PDD. Given this, agents that affect microglial activation could have an influence on disease progression.

Bibliographic metadata

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Content type:
Publication type:
Publication form:
Published date:
Abbreviated journal title:
ISSN:
Place of publication:
England
Volume:
38
Issue:
6
Pagination:
938-49
Digital Object Identifier:
10.1038/npp.2012.255
Pubmed Identifier:
23303049
Pii Identifier:
npp2012255
Access state:
Active

Institutional metadata

University researcher(s):

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:197276
Created by:
Hinz, Rainer
Created:
10th June, 2013, 08:59:52
Last modified by:
Hinz, Rainer
Last modified:
10th June, 2013, 09:04:12

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