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Lookup NU author(s): Rob Atkinson, Professor David BrooksORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Objective: To investigate the influence of microglial activation in the early stages of Alzheimer’s disease trajectory, we evaluated the relationship between microglial activation and grey matter volume and hippocampal volume in MCI subjects. Methods: In this study, fifty-five subjects (37 early stages MCI and 18 controls) underwent [11C]PBR28 PET, a marker of microglial activation; volumetric MRI to assess grey matter volume and hippocampal volume; along with neurological and neuropsychometric evaluation. [11C]PBR28 VT (volume of distribution) was calculated using arterial input function and Logan Graphical analysis. Grey matter volume and hippocampal volumes were calculated from MRI for each subject. Voxel-wise correlations and biological parametric mapping analysis were performed using Statistical parametric mapping software. Amyloid load was assessed using [18F]Flutemetamol PET. Results: [11C]PBR28 VT in different cortical areas positively correlated with the grey matter volume in both amyloid positive and negative MCI. Additionally, hippocampal volume demonstrated significant positive correlations with cortical [11C]PBR28 Logan VT. Conclusions: In this study for the first time, in vivo, we have demonstrated that microglial activation quantified using [11C]PBR28 PET was associated with higher grey matter volume and higher hippocampal volume in MCI subjects. This may suggest that microglial activation may not always be associated with neuronal damage, and indeed it may have beneficial effect in early stages of Alzheimer’s trajectory. While further longitudinal studies are necessary, these findings have huge implications on novel therapeutic strategies influencing microglial activation.
Author(s): Femminella GD, Dani M, Wood M, Fan Z, Calsolaro V, Atkinson R, Hinz R, Brooks DJ, Edison P
Publication type: Article
Publication status: Published
Journal: Neurology
Year: 2019
Volume: 92
Issue: 12
Pages: e1331-e1343
Print publication date: 19/03/2019
Online publication date: 22/02/2019
Acceptance date: 14/11/2018
Date deposited: 31/10/2018
ISSN (print): 0028-3878
ISSN (electronic): 1526-632X
Publisher: Lippincott Williams & Wilkins
URL: https://doi.org/10.1212/WNL.0000000000007133
DOI: 10.1212/WNL.0000000000007133
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