Microglial activation in early Alzheimer trajectory is associated with higher grey matter volume
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Published version
Author(s)
Type
Journal Article
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 grey matter volume and hippocampal volume in MCI patients.
Methods: In this study, fifty-five participants (37 early stages MCI and 18 controls) underwent [11C]PBR28 PET, a marker of microglial activation; volumetric MRI to evaluate grey 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. Grey matter volume and hippocampal volumes were calculated from MRI for each subject. 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 grey matter volume in both amyloid positive and negative MCI. Additionally, 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 grey matter volume and higher hippocampal volume in MCI patients. 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 significant implications on therapeutic strategies targeting microglial activation.
Methods: In this study, fifty-five participants (37 early stages MCI and 18 controls) underwent [11C]PBR28 PET, a marker of microglial activation; volumetric MRI to evaluate grey 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. Grey matter volume and hippocampal volumes were calculated from MRI for each subject. 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 grey matter volume in both amyloid positive and negative MCI. Additionally, 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 grey matter volume and higher hippocampal volume in MCI patients. 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 significant implications on therapeutic strategies targeting microglial activation.
Date Issued
2019-03-01
Date Acceptance
2018-10-14
Citation
Neurology, 2019, 92 (12), pp.e1331-e1343
ISSN
1526-632X
Publisher
American Academy of Neurology
Start Page
e1331
End Page
e1343
Journal / Book Title
Neurology
Volume
92
Issue
12
Copyright Statement
© 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 (CC BY), which permits unrestricted use, distribution, and reproduction in anymedium, provided the original work is properly cited.
Sponsor
Alzheimer's Research UK (ARUK)
Medical Research Council (MRC)
Medical Research Council (MRC)
Grant Number
ART/PG2005/3
G84/6523
G1100810
Subjects
Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences & Neurology
MILD COGNITIVE IMPAIRMENT
POSITRON-EMISSION-TOMOGRAPHY
PROTEIN 18 KDA
PARKINSONS-DISEASE
NEURONAL FUNCTION
MOUSE MODEL
BRAIN
NEUROINFLAMMATION
PET
INFLAMMATION
1103 Clinical Sciences
1109 Neurosciences
1702 Cognitive Sciences
Neurology & Neurosurgery
Publication Status
Published
Date Publish Online
2019-02-22