@article{e10ea73d223142b5936b9a3c8bcfbd91,
title = "Relationship between astrocyte reactivity, using novel 11C-BU99008 PET, and glucose metabolism, grey matter volume and amyloid load in cognitively impaired individuals",
abstract = "Post mortem neuropathology suggests that astrocyte reactivity may play a significant role in neurodegeneration in Alzheimers disease. We explored this in vivo using multimodal PET and MRI imaging. Twenty subjects (11 older, cognitively impaired subjects and 9 age-matched healthy controls) underwent brain scanning using the novel reactive astrocyte PET tracer 11C-BU99008, 18F-FDG and 18F-florbetaben PET, and T1-weighted MRI. Differences between cognitively impaired subjects and healthy controls in voxel-wise levels of astrocyte reactivity, glucose metabolism and grey matter volume were explored, and their relationship to each other was assessed using Biological Parametric Mapping (BPM). A{beta}-positive cognitively impaired subjects showed greater brain astrocyte reactivity, except in the temporal lobe, with further increased astrocyte reactivity in Mild Cognitive Impairment compared to Alzheimers subjects in the cingulate cortices. BPM correlations revealed regions which showed reduced 11C-BU99008 uptake in A{beta}-positive cognitively impaired subjects, such as the temporal lobe, also showed reduced 18F-FDG uptake and grey matter volume. BPM analysis also revealed a regionally-dynamic relationship between astrocyte reactivity and amyloid uptake: increased amyloid load in cortical association areas of the temporal lobe and cingulate cortices was associated with reduced astrocyte reactivity, whilst increased amyloid uptake in primary motor and sensory areas (in which amyloid load occurs later) was associated with increased astrocyte reactivity. These novel observations add to the hypothesis that while astrocyte reactivity may be triggered by early A{beta}-deposition, sustained pro-inflammatory astrocyte reactivity with greater amyloid deposition may lead to astrocyte dystrophy and amyloid-associated neuropathology such as grey matter atrophy and glucose hypometabolism.",
keywords = "neurology",
author = "Livingston, {N. R.} and V. Calsolaro and R. Hinz and J. Nowell and S. Raza and S. Gentleman and Tyacke, {R. J.} and Venkataraman, {A. V.} and R. Perneczky and Gunn, {R. N.} and Rabiner, {E. A.} and Parker, {C. A.} and Murphy, {P. S.} and Wren, {P. B.} and Nutt, {D. J.} and Matthews, {P. M.} and P. Edison and Paul Edison",
note = "Funding Information: The authors thank Invicro Centre for Imaging Sciences for the provision of11C-BU99008, scanning and blood analysis equipment. The authors also thank Piramal Life Sciences/Life Molecular Imaging for providing the18F-florbetaben and permission to acquire unlabelled florbetaben. We thank Dementia Platform UK (DPUK) and GSK for the generous funding for this project. This research was co-funded by the NIHR Imperial Biomedical Research Centre and was supported by the NIHR Imperial Clinical Research Facility. The views expressed are those of the authors and not necessarily those of NHS, the NIHR nor the Department of Health. The study was funded by the Dementia Platform UK and the National Institutes of Health Research Imperial College Healthcare Trust Biomedical Research Centre. PE was funded by the Medical Research Council and now by Higher Education Funding Council for England (HEFCE). He has also received grants from Alzheimer{\textquoteright}s Research, UK, Alzheimer{\textquoteright}s Drug Discovery Foundation, Alzheimer{\textquoteright}s Society, UK, Alzheimer{\textquoteright}s association, US, Medical Research Council, UK, Novo Nordisk, Piramal Life Sciences and GE Healthcare. PMM gratefully acknowledges generous support from Edmond J Safra Foundation and Lily Safra, the NIHR Investigator programme and the UK Dementia Research Institute. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = apr,
doi = "10.1101/2021.08.10.21261690",
language = "English",
volume = "27",
pages = "2019--2029",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Springer Nature [academic journals on nature.com]",
number = "4",
}
