Relationship between astrocyte reactivity, using novel 11C-BU99008 PET, and glucose metabolism, grey matter volume and amyloid load in cognitively impaired individuals

N. R. Livingston, V. Calsolaro, R. Hinz, J. Nowell, S. Raza, S. Gentleman, R. J. Tyacke, A. V. Venkataraman, R. Perneczky, R. N. Gunn, E. A. Rabiner, C. A. Parker, P. S. Murphy, P. B. Wren, D. J. Nutt, P. M. Matthews, P. Edison, Paul Edison*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)2019-2029
Number of pages11
JournalMolecular Psychiatry
Volume27
Issue number4
DOIs
Publication statusPublished - Apr 2022

Keywords

  • neurology

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