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Microglial activation in early Alzheimer trajectory is associated with higher gray matter volume

Femminella, GD; Dani, M; Wood, M; Fan, Z; Calsolaro, V; Atkinson, R; Edginton, T; ... Edison, P; + view all (2019) Microglial activation in early Alzheimer trajectory is associated with higher gray matter volume. Neurology , 92 (12) e1331-e1343. 10.1212/WNL.0000000000007133. Green open access

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Abstract

OBJECTIVE: To investigate the influence of microglial activation in the early stages of Alzheimer's disease trajectory, we assessed the relationship between microglial activation and gray matter volume and hippocampal volume in patients with mild cognitive impairment (MCI). METHODS: In this study, 55 participants (37 with early stages of MCI and 18 controls) underwent [11C]PBR28 PET, a marker of microglial activation; volumetric MRI to evaluate gray matter and hippocampal volumes as well as clinical and neuropsychometric evaluation. [11C]PBR28 VT (volume of distribution) was calculated using arterial input function and Logan graphical analysis. Gray matter volume and hippocampal volumes were calculated from MRI for each participant. Statistical parametric mapping software was used to perform voxel-wise correlations and biological parametric mapping analysis. Amyloid status was assessed using [18F]flutemetamol PET. RESULTS: Higher [11C]PBR28 VT in different cortical areas correlated with higher gray matter volume in both amyloid-positive and -negative MCI. In addition, higher hippocampal volume correlated with higher cortical [11C]PBR28 Logan VT. CONCLUSIONS: In this in vivo study, we have demonstrated that microglial activation quantified using [11C]PBR28 PET was associated with higher gray matter volume and higher hippocampal volume in patients with MCI. This might suggest that microglial activation may not always be associated with neuronal damage, and indeed it may have a beneficial effect in the early stages of the Alzheimer trajectory. While further longitudinal studies are necessary, these findings have significant implications on therapeutic strategies targeting microglial activation.

Type: Article
Title: Microglial activation in early Alzheimer trajectory is associated with higher gray matter volume
Open access status: An open access version is available from UCL Discovery
DOI: 10.1212/WNL.0000000000007133
Publisher version: https://doi.org/10.1212/WNL.0000000000007133
Language: English
Additional information: © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (https://creativecommons.org/licenses/by/4.0/).
Keywords: Alzheimer's disease, MRI, PET, MCI (mild cognitive impairment)
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences > Institute of Cognitive Neuroscience
URI: https://discovery.ucl.ac.uk/id/eprint/10071981
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