“¹¹C-BU99008 is a novel positron emission tomography (PET) tracer that enables selective imaging of astrocyte reactivity in vivo,” begins the abstract of a new study publishes as Open Access in Molecular Psychiatry. The study used this tracer to look at the relationship between astrocyte reactivity and its relationship to amyloid beta load in late-stage Alzheimer’s patients.

Valeria Calsolaro, et al, verified a new tool available to researchers for the study of Alzheimer’s disease. “This proof-of-concept study provides direct evidence that ¹¹C-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.”

Source:

Calsolaro, V., Matthews, P.M., Donat, C.K. et al. “Astrocyte reactivity with late-onset cognitive impairment assessed in vivo using 11C-BU99008 PET and its relationship with amyloid load.” Mol Psychiatry (2021). https://doi.org/10.1038/s41380-021-01193-z Accessed: August 2, 2021

Open Access article published under the Creative Commons Attribution 4.0 International License. Selected text excerpts were quoted directly and were not changed. Selected images were converted from webp format to png format; figure 4 was scaled down by 50% but not otherwise altered. View licensing information at: https://creativecommons.org/licenses/by/4.0/

Figure 4: A Greater 3H-BU99008 binding around Aβ plaques in AD brain tissue sections. Representative autoradiographs showing 3H-BU99008 total (left panel) and non-specific binding (centre panel; determined with 10 µM BU224) in 12 µm frontal cortex sections of the human brain (AD and age-matched controls). Standards (ARC 123B) represent a linear range of radioactivity. Immunohistochemistry for total Aβ (1 µg/mL pan-anti-Aβ, MOAB-2, clone 6C3, right panel) shows spatial distribution of plaques. White arrows point to high-intensity binding of 3H-BU99008 in the vicinity of plaques (black arrows), as magnified inserts show. B 3H-BU99008 binding is increased in AD brain sections relative to control brain. Comparative quantitative analysis of specific binding of 3H-BU99008 in grey and white matter (when identifiable) or total section of 12 µm frontal cortex sections (AD with Braak stages 5–6 and controls). Binding of 3H-BU99008 in the total sections from AD cases is significantly higher (unpaired t-test) than that in controls. Data is mean (±SD) from triplicates; AD: n = 6, Control: n = 5. C Non-specific binding is not different between AD and control brain sections. Quantitative analysis of non-specific binding, showing no difference between brain sections from AD and controls. Increased specific binding in AD (A/B) sections relative to controls therefore is not caused by differences in non-specific binding. D 3H-BU99008 binding colocalised with GFAP staining. Autoradiograph showing 3H-BU99008 total binding (left panel) and non-specific binding (centre panel; determined with 10 µM BU224) in 14 µm frontal cortex sections of the human brain (Braak stage 6). Standards (ARC 123B) represent a linear range of radioactivity. Immunohistochemistry for GFAP (right panel) shows spatial distribution of an astrocytic marker. Magnifications of 3H-BU99008 binding and GFAP staining are shown in the panels. Solid red arrows point to high-intensity 3H-BU99008 binding and corresponding areas of GFAP staining. E, F Common Aβ tracers do not displace 3H-BU99008 binding. Autoradiograph showing 3H-BU99008 total binding (left upper panel) and non-specific binding (left lower panel; determined with 10 µM BU224) in 14 µm frontal cortex sections of the human brain (Braak stage 2). Standards (ARC 123B) represent a linear range of radioactivity. Upper/lower right row shows binding of 3H-BU99008 in the presence of two commonly unlabelled PiB and Florbetaben, two commonly used Aβ tracers in ascending concentrations, showing no displacement. Quantitative analysis of specific binding (E) in the grey and white matter and in the presence of unlabelled PiB and Florbetaben (10–10000 nMol/L) in 14 µm frontal cortex sections (Braak stage 2). Quantification indicates that high-intensity 3H-BU99008 accumulation around plaques is likely not caused by binding to common Aβ-binding sites.