UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

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

Dani, M; Wood, M; Mizoguchi, R; Fan, Z; Walker, Z; Morgan, R; Hinz, R; ... Edison, P; + view all (2018) Microglial activation correlates in vivo with both tau and amyloid in Alzheimer’s disease. BRAIN. A Journal of Neurology , 141 (9) pp. 2740-2754. 10.1093/brain/awy188. Green open access

[thumbnail of Walker_Microglial activation correlates in vivo with both tau and amyloid in Alzheimer's disease_AAM.pdf]
Preview
Text
Walker_Microglial activation correlates in vivo with both tau and amyloid in Alzheimer's disease_AAM.pdf - Accepted Version

Download (537kB) | Preview

Abstract

Alzheimer’s disease is characterized by the histopathological presence of amyloid-β plaques and tau-containing neurofibrillary tangles. Microglial activation is also a recognized 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 (19 healthy controls, 16 mild cognitive impairment and 16 Alzheimer’s disease subjects) participated in the study. All subjects had neuropsychometric testing, MRI, amyloid (¹⁸F-flutemetamol), and microglial (¹¹C-PBR28) PET. All subjects with mild cognitive impairment and Alzheimer’s disease and eight of the controls had tau (¹⁸F-AV1451) PET. ¹¹C-PBR28 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 standardized uptake value ratio maps. Biological parametric mapping 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 mild cognitive impairment (amyloid-positive and amyloid-negative) and Alzheimer’s disease subjects. The correlations were stronger in Alzheimer’s disease than in mild cognitive impairment, 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 mild cognitive impairment 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.

Type: Article
Title: Microglial activation correlates in vivo with both tau and amyloid in Alzheimer’s disease
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/brain/awy188
Publisher version: https://doi.org/10.1093/brain/awy188
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: tau, amyloid, microglia, PET, imaging, Alzheimer's disease
UCL classification: UCL
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 > Division of Psychiatry
URI: https://discovery.ucl.ac.uk/id/eprint/10072309
Downloads since deposit
74Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item