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

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.

Publication metadata

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


DOI: 10.1212/WNL.0000000000007133


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