In vitro Characterization of the Regional Binding Distribution of Amyloid PET Tracer Florbetaben and the Glia Tracers Deprenyl and PK11195 in Autopsy Alzheimer's Brain Tissue
| Autor: | Ruiqing, Ni, Jennie, Röjdner, Larysa, Voytenko, Thomas, Dyrks, Andrea, Thiele, Amelia, Marutle, Agneta, Nordberg |
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| Rok vydání: | 2021 |
| Předmět: |
Male
positron emission tomography microglia Plaque Amyloid Alzheimer Disease Selegiline Stilbenes Humans Gliosis Aged Aged 80 and over Amyloid beta-Peptides Aniline Compounds astrocytes Brain Middle Aged Isoquinolines glial fibrillary acid protein Case-Control Studies Positron-Emission Tomography amyloid-beta peptides monoamine oxidase B Female Autopsy Neuroglia Alzheimer’s disease Research Article |
| Zdroj: | Journal of Alzheimer's Disease |
| ISSN: | 1875-8908 |
| Popis: | Background: Emerging evidence indicates a central role of gliosis in Alzheimer’s disease (AD) pathophysiology. However, the regional distribution and interaction of astrogliosis and microgliosis in association with amyloid-β (Aβ) still remain uncertain. Objective: Here we studied the pathological profiles in autopsy AD brain by using specific imaging tracers. Methods: Autopsy brain tissues of AD (n = 15, age 70.4±8.5 years) and control cases (n = 12, age 76.6±10.9) were examined with homogenate binding assays, autoradiography for Aβ plaques (3H-florbetaben/3H-PIB), astrogliosis (3H-L-deprenyl), and microgliosis (3H-PK11195/3H-FEMPA), as well as immunoassays. Results: In vitro saturation analysis revealed high-affinity binding sites of 3H-florbetaben, 3H-L-deprenyl, and 3H-PK11195/3H-FEMPA in the frontal cortex of AD cases. In vitro 3H-florbetaben binding increased across cortical and subcortical regions of AD compared to control with the highest binding in the frontal and parietal cortices. The in vitro 3H-L-deprenyl binding showed highest binding in the hippocampus (dentate gyrus) followed by cortical and subcortical regions of AD while the GFAP expression was upregulated only in the hippocampus compared to control. The in vitro 3H-PK11195 binding was solely increased in the parietal cortex and the hippocampus of AD compared to control. The 3H-florbetaben binding positively correlated with the 3H-L-deprenyl binding in the hippocampus and parietal cortex of AD and controls. Similarly, a positive correlation was observed between 3H-florbetaben binding and GFAP expression in hippocampus of AD and control. Conclusion: The use of multi-imaging tracers revealed different regional pattern of changes in autopsy AD brain with respect to amyloid plaque pathology versus astrogliosis and microgliosis. |
| Databáze: | OpenAIRE |
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