Astrocyte reactivity with late-onset cognitive impairment assessed in vivo using 11 C-BU99008 PET and its relationship with amyloid load.

Autor: Calsolaro V; Department of Brain Sciences, Imperial College London, London, UK., Matthews PM; Department of Brain Sciences, Imperial College London, London, UK.; UK Dementia Research Institute, Imperial College London, London, UK., Donat CK; Department of Brain Sciences, Imperial College London, London, UK.; Centre for Blast Injury Studies, Imperial College London, London, UK., Livingston NR; Department of Brain Sciences, Imperial College London, London, UK., Femminella GD; Department of Brain Sciences, Imperial College London, London, UK., Guedes SS; Department of Brain Sciences, Imperial College London, London, UK., Myers J; Department of Brain Sciences, Imperial College London, London, UK., Fan Z; Department of Brain Sciences, Imperial College London, London, UK., Tyacke RJ; Department of Brain Sciences, Imperial College London, London, UK., Venkataraman AV; Department of Brain Sciences, Imperial College London, London, UK., Perneczky R; Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.; German Centre for Neurodegenerative Disorders (DZNE), Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.; Ageing Epidemiology Research Unit (AGE), School of Public Health, Imperial College London, London, UK., Gunn R; Department of Brain Sciences, Imperial College London, London, UK.; Invicro, London, UK., Rabiner EA; Invicro, London, UK.; King's College London, London, UK., Gentleman S; Department of Brain Sciences, Imperial College London, London, UK., Parker CA; Department of Brain Sciences, Imperial College London, London, UK.; GlaxoSmithKline, Stevenage, UK., Murphy PS; GlaxoSmithKline, Stevenage, UK., Wren PB; GlaxoSmithKline, Stevenage, UK., Hinz R; Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK., Sastre M; Department of Brain Sciences, Imperial College London, London, UK., Nutt DJ; Department of Brain Sciences, Imperial College London, London, UK., Edison P; Department of Brain Sciences, Imperial College London, London, UK. paul.edison@imperial.ac.uk.; Cardiff University, Cardiff, Wales, United Kingdom. paul.edison@imperial.ac.uk.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2021 Oct; Vol. 26 (10), pp. 5848-5855. Date of Electronic Publication: 2021 Jul 15.
DOI: 10.1038/s41380-021-01193-z
Abstrakt: 11 C-BU99008 is a novel positron emission tomography (PET) tracer that enables selective imaging of astrocyte reactivity in vivo. To explore astrocyte reactivity associated with Alzheimer's disease, 11 older, cognitively impaired (CI) subjects and 9 age-matched healthy controls (HC) underwent 3T magnetic resonance imaging (MRI), 18 F-florbetaben and 11 C-BU99008 PET. The 8 amyloid (Aβ)-positive CI subjects had higher 11 C-BU99008 uptake relative to HC across the whole brain, but particularly in frontal, temporal, medial temporal and occipital lobes. Biological parametric mapping demonstrated a positive voxel-wise neuroanatomical correlation between 11 C-BU99008 and 18 F-florbetaben. Autoradiography using 3 H-BU99008 with post-mortem Alzheimer's brains confirmed through visual assessment that increased 3 H-BU99008 binding localised with the astrocyte protein glial fibrillary acid protein and was not displaced by PiB or florbetaben. This proof-of-concept study provides direct evidence that 11 C-BU99008 can measure in vivo astrocyte reactivity in people with late-life cognitive impairment and Alzheimer's disease. Our results confirm that increased astrocyte reactivity is found particularly in cortical regions with high Aβ load. Future studies now can explore how clinical expression of disease varies with astrocyte reactivity.
(© 2021. The Author(s).)
Databáze: MEDLINE
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