Microglial activation facilitates Aβ plaque removal following intracranial anti-Aβ antibody administration

Donna M Wilcock; Sanjay K Munireddy; Arnon Rosenthal; Kenneth E Ugen; Marcia N Gordon; Dave Morgan

Neurobiology of Disease (Feb 2004)

Microglial activation facilitates Aβ plaque removal following intracranial anti-Aβ antibody administration

Donna M Wilcock,
Sanjay K Munireddy,
Arnon Rosenthal,
Kenneth E Ugen,
Marcia N Gordon,
Dave Morgan

Affiliations

Donna M Wilcock: Department of Pharmacology, Alzheimer's Research Laboratory, University of South Florida, Tampa, FL 33612, USA; Rinat Neuroscience Corporation, Palo Alto, CA 94304, USA; Department of Medical Microbiology and Immunology, Alzheimer's Research Laboratory, University of South Florida, Tampa, FL 33612, USA
Sanjay K Munireddy: Department of Pharmacology, Alzheimer's Research Laboratory, University of South Florida, Tampa, FL 33612, USA; Rinat Neuroscience Corporation, Palo Alto, CA 94304, USA; Department of Medical Microbiology and Immunology, Alzheimer's Research Laboratory, University of South Florida, Tampa, FL 33612, USA
Arnon Rosenthal: Department of Pharmacology, Alzheimer's Research Laboratory, University of South Florida, Tampa, FL 33612, USA; Rinat Neuroscience Corporation, Palo Alto, CA 94304, USA; Department of Medical Microbiology and Immunology, Alzheimer's Research Laboratory, University of South Florida, Tampa, FL 33612, USA
Kenneth E Ugen: Department of Pharmacology, Alzheimer's Research Laboratory, University of South Florida, Tampa, FL 33612, USA; Rinat Neuroscience Corporation, Palo Alto, CA 94304, USA; Department of Medical Microbiology and Immunology, Alzheimer's Research Laboratory, University of South Florida, Tampa, FL 33612, USA
Marcia N Gordon: Department of Pharmacology, Alzheimer's Research Laboratory, University of South Florida, Tampa, FL 33612, USA; Rinat Neuroscience Corporation, Palo Alto, CA 94304, USA; Department of Medical Microbiology and Immunology, Alzheimer's Research Laboratory, University of South Florida, Tampa, FL 33612, USA
Dave Morgan: Department of Pharmacology, Alzheimer's Research Laboratory, University of South Florida, Tampa, FL 33612, USA; Rinat Neuroscience Corporation, Palo Alto, CA 94304, USA; Department of Medical Microbiology and Immunology, Alzheimer's Research Laboratory, University of South Florida, Tampa, FL 33612, USA

Journal volume & issue: Vol. 15, no. 1
pp. 11 – 20

Abstract

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The mechanisms by which anti-Aβ antibodies clear amyloid plaques in Aβ depositing transgenic mice are unclear. In the current study, we demonstrate that inhibition of anti-Aβ antibody-induced microglial activation with anti-inflammatory drugs, such as dexamethasone, inhibits removal of fibrillar amyloid deposits. We also show that anti-Aβ F(ab′)2 fragments fail to activate microglia and are less efficient in removing fibrillar amyloid than the corresponding complete IgG. Diffuse Aβ deposits are cleared by antibodies under all circumstances. These data suggest that microglial activation is necessary for efficient removal of compact amyloid deposits with immunotherapy. Inhibition of this activation may result in an impaired clinical response to vaccination against Aβ.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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Abstract

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