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

Livingston, Nicholas R.; Calsolaro, Valeria; Hinz, Rainer; Nowell, Joseph; Raza, Sanara; Gentleman, Steve; Tyacke, Robin J.; Myers, Jim; Venkataraman, Ashwin V.; Perneczky, Robert; Gunn, Roger N.; Rabiner, Eugenii A.; Parker, Christine A.; Murphy, Philip S.; Wren, Paul B.; Nutt, David J.; Matthews, Paul M. und Edison, Paul (2022): Relationship between astrocyte reactivity, using novel C-11-BU99008 PET, and glucose metabolism, grey matter volume and amyloid load in cognitively impaired individuals. In: Molecular Psychiatry, Bd. 27, Nr. 4: S. 2019-2029

Abstract

Post mortem neuropathology suggests that astrocyte reactivity may play a significant role in neurodegeneration in Alzheimer's disease. We explored this in vivo using multimodal PET and MRI imaging. Twenty subjects (11 older, cognitively impaired patients and 9 age-matched healthy controls) underwent brain scanning using the novel reactive astrocyte PET tracer C-11-BU99008, F-18-FDG and F-18-florbetaben PET, and T1-weighted MRI. Differences between cognitively impaired patients and healthy controls in regional and voxel-wise levels of astrocyte reactivity, glucose metabolism, grey matter volume and amyloid load were explored, and their relationship to each other was assessed using Biological Parametric Mapping (BPM). Amyloid beta (A beta)-positive patients showed greater C-11-BU99008 uptake compared to controls, except in the temporal lobe, whilst further increased C-11-BU99008 uptake was observed in Mild Cognitive Impairment subjects compared to those with Alzheimer's disease in the frontal, temporal and cingulate cortices. BPM correlations revealed that regions which showed reduced C-11-BU99008 uptake in A beta-positive patients compared to controls, such as the temporal lobe, also showed reduced F-18-FDG uptake and grey matter volume, although the correlations with F-18-FDG uptake were not replicated in the ROI analysis. 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(11)C-BU99008 uptake, whilst increased amyloid uptake in primary motor and sensory areas (in which amyloid deposition occurs later) was associated with increased(11)C-BU99008 uptake. 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, although the evidence for glucose hypometabolism here is less strong.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1359-4184
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198