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Microglial activation correlates in vivo with both tau and amyloid in Alzheimer’s disease

Lookup NU author(s): Professor David BrooksORCiD



This is the authors' accepted manuscript of an article that has been published in its final definitive form by Oxford University Press, 2018.

For re-use rights please refer to the publisher's terms and conditions.


Alzheimer’s disease is characterised by the histopathological presence of β-amyloid plaques and tau containing neurofibrillary tangles. Microglial activation is also a recognised pathological component. The relationship between microglial activation and protein aggregation is still debated. We investigated the relationship between amyloid plaques, tau tangles and activated microglia using PET imaging. Fifty-one subjects (nineteen healthy controls, sixteen mild cognitive impairment (MCI) and sixteen Alzheimer’s disease subjects) participated in the study. All subjects had neuropsychometric testing, magnetic resonance imaging (MRI), amyloid (18F-flutemetamol), and microglial (11C-PBR28) PET. All MCI and Alzheimer’s disease (AD) subjects and eight of the controls had tau (18F-AV1451) PET. 11CPBR28 PET was analysed using Logan graphical analysis with an arterial plasma input function, while 18F-flutemetamol and 18F-AV1451 PET were analysed as target: cerebellar ratios to create parametric Standardised Uptake Value Ratio (SUVR) maps. Biological parametric mapping (BPM) in the Statistical Parametric Mapping platform was used to examine correlations between uptake of tracers at a voxel-level. There were significant widespread clusters of positive correlation between levels of microglial activation and tau aggregation in both the MCI (amyloid positive and amyloid negative) and AD subjects. The correlations were stronger in AD than in MCI, suggesting that these pathologies increase together as disease progresses. Levels of microglial activation and amyloid deposition were also correlated, although in a different spatial distribution; correlations were stronger in MCI than Alzheimer’s subjects, in line with a plateauing of amyloid load with disease progression. Clusters of positive correlations between microglial activation and protein aggregation often targeted similar areas of association cortex, indicating that all three processes are present in specific vulnerable brain areas. For the first time using PET imaging, we show that microglial activation can correlate with both tau aggregation and amyloid deposition. This confirms the complex relationship between these processes. These results suggest that preventative treatment for Alzheimer’s disease should target all three processes.

Publication metadata

Author(s): Dani M, Wood M, Mizoguchi R, Fan Z, Walker Z, Morgan R, Hinz R, Biju M, Kuruvilla T, Brooks DJ, Edison P

Publication type: Article

Publication status: Published

Journal: Brain

Year: 2018

Volume: 141

Issue: 9

Pages: 2740-2754

Print publication date: 01/09/2018

Online publication date: 20/07/2018

Acceptance date: 29/05/2018

Date deposited: 30/05/2018

ISSN (print): 0006-8950

ISSN (electronic): 1460-2156

Publisher: Oxford University Press


DOI: 10.1093/brain/awy188


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