Rapid microglial response around amyloid pathology following systemic anti-Aβ antibody administration in PDAPP mice
| Autor: | David M. Holtzman, Mary Beth Finn, Bradley T. Hyman, Maia Parsadanian, Melanie Meyer-Luehmann, Jessica Koenigsknecht-Talboo, Brian J. Bacskai, Monica Garcia-Alloza |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Amyloid
Green Fluorescent Proteins CX3C Chemokine Receptor 1 Cell Count Mice Transgenic Plaque Amyloid Alkenes Article Antibodies Amyloid beta-Protein Precursor Mice Alzheimer Disease Cell Movement CX3CR1 Stilbenes medicine Benzene Derivatives Animals Senile plaques Microglia biology business.industry General Neuroscience Calcium-Binding Proteins Microfilament Proteins Age Factors medicine.disease Cerebral Amyloid Angiopathy Disease Models Animal medicine.anatomical_structure Immunology Systemic administration biology.protein Leukocyte Common Antigens Receptors Chemokine Cerebral amyloid angiopathy Alzheimer's disease Antibody business |
| Popis: | Aggregation of amyloid-β (Aβ) peptide in the brain in the form of neuritic plaques and cerebral amyloid angiopathy (CAA) is a key feature of Alzheimer's disease (AD). Microglial cells surround aggregated Aβ and are believed to play a role in AD pathogenesis. A therapy for AD that has entered clinical trials is the administration of anti-Aβ antibodies. One mechanism by which certain anti-Aβ antibodies have been proposed to exert their effects is via antibody-mediated microglial activation. Whether, when, or to what extent microglial activation occurs after systemic administration of anti-Aβ antibodies has not been fully assessed. We administered an anti-Aβ antibody (m3D6) that binds aggregated Aβ to PDAPP mice, an AD mouse model that was bred to contain fluorescent microglia. Three days after systemic administration of m3D6, there was a marked increase in both the number of microglial cells and processes per cell visualizedin vivoby multiphoton microscopy. These changes required the Fc domain of m3D6 and were not observed with an antibody specific to soluble Aβ. These findings demonstrate that some effects of antibodies that recognize aggregated Aβ are rapid, involve microglia, and provide insight into the mechanism of action of a specific passive immunotherapy for AD. |
| Databáze: | OpenAIRE |
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