Mechanisms of [beta]-amyloid clearance by anti-a[beta] antibody therapy. [electronic resource] / Wilcock, Donna Marie. [Tampa, Fla.] : University of South Florida, 2004. eng ABSTRACT: Alzheimers disease (AD) is defined as a progressive neurodegenerative disorder that gradually destroys a persons memory and ability to learn. There are three pathological hallmarks of the disease which are necessary for diagnosis of AD, these are; extracellular amyloid plaques composed of [beta]-amyloid (A[beta]) protein, intracellular neurofibrillary tangles and neuronal loss. Amyloid plaques exist as both compact deposits which stain with Congo red and more numerous diffuse deposits. Active immunization against A[beta] 1-42 or passive immunization with monoclonal anti-A[beta] antibodies reduces amyloid deposition and improves cognition in APP transgenic mice.Over several studies of active immunization in APP+PS1 transgenic mice we showed a strong correlation between reduction of compact amyloid deposits and the degree of microglial activation suggesting a potential role of microglia in the removal of A[beta]. Injection of anti-A[beta] antibodies into the frontal cortex and hippocampus of aged APP transgenic mice revealed an early phase of A[beta] removal which was removal of only diffuse amyloid deposits with no associated activation of microglia. A later phase was the removal of compact amyloid deposits. This was associated with significant activation of microglia. Prevention of this microglial activation by anti-A[beta] F(ab)2 fragments or its inhibition by dexamethasone also precluded the removal of compact amyloid deposits but did not affect the removal of the diffuse deposits. Systemic injection of anti-A[beta] antibodies weekly over a period of 1, 2, 3 and 5 months transiently activated microglia associated with the removal of compact amyloid deposits and elevated plasma A[beta], suggesting a peripheral mechanism contributes to removal of brain A[beta]. Thesis (Ph.D.)--University of South Florida, 2004. Includes bibliographical references. Text (Electronic thesis) in PDF format. System requirements: World Wide Web browser and PDF reader. Mode of access: World Wide Web. ABSTRACT: Alzheimers disease (AD) is defined as a progressive neurodegenerative disorder that gradually destroys a persons memory and ability to learn. There are three pathological hallmarks of the disease which are necessary for diagnosis of AD, these are; extracellular amyloid plaques composed of [beta]-amyloid (A[beta]) protein, intracellular neurofibrillary tangles and neuronal loss. Amyloid plaques exist as both compact deposits which stain with Congo red and more numerous diffuse deposits. Active immunization against A[beta] 1-42 or passive immunization with monoclonal anti-A[beta] antibodies reduces amyloid deposition and improves cognition in APP transgenic mice.Over several studies of active immunization in APP+PS1 transgenic mice we showed a strong correlation between reduction of compact amyloid deposits and the degree of microglial activation suggesting a potential role of microglia in the removal of A[beta]. Injection of anti-A[beta] antibodies into the frontal cortex and hippocampus of aged APP transgenic mice revealed an early phase of A[beta] removal which was removal of only diffuse amyloid deposits with no associated activation of microglia. A later phase was the removal of compact amyloid deposits. This was associated with significant activation of microglia. Prevention of this microglial activation by anti-A[beta] F(ab)2 fragments or its inhibition by dexamethasone also precluded the removal of compact amyloid deposits but did not affect the removal of the diffuse deposits. Systemic injection of anti-A[beta] antibodies weekly over a period of 1, 2, 3 and 5 months transiently activated microglia associated with the removal of compact amyloid deposits and elevated plasma A[beta], suggesting a peripheral mechanism contributes to removal of brain A[beta]. Adviser: David Morgan Ph.D. Immunization. Transgenic mice. Inflammation. Alzheimers disease.
Mechanisms of [beta]-amyloid clearance by anti-a[beta] antibody therapy. [electronic resource] /
Wilcock, Donna Marie.
[Tampa, Fla.] : University of South Florida,
2004.
eng
ABSTRACT: Alzheimers disease (AD) is defined as a progressive neurodegenerative disorder that gradually destroys a persons memory and ability to learn. There are three pathological hallmarks of the disease which are necessary for diagnosis of AD, these are; extracellular amyloid plaques composed of [beta]-amyloid (A[beta]) protein, intracellular neurofibrillary tangles and neuronal loss. Amyloid plaques exist as both compact deposits which stain with Congo red and more numerous diffuse deposits. Active immunization against A[beta] 1-42 or passive immunization with monoclonal anti-A[beta] antibodies reduces amyloid deposition and improves cognition in APP transgenic mice.Over several studies of active immunization in APP+PS1 transgenic mice we showed a strong correlation between reduction of compact amyloid deposits and the degree of microglial activation suggesting a potential role of microglia in the removal of A[beta].
Injection of anti-A[beta] antibodies into the frontal cortex and hippocampus of aged APP transgenic mice revealed an early phase of A[beta] removal which was removal of only diffuse amyloid deposits with no associated activation of microglia. A later phase was the removal of compact amyloid deposits. This was associated with significant activation of microglia. Prevention of this microglial activation by anti-A[beta] F(ab)2 fragments or its inhibition by dexamethasone also precluded the removal of compact amyloid deposits but did not affect the removal of the diffuse deposits. Systemic injection of anti-A[beta] antibodies weekly over a period of 1, 2, 3 and 5 months transiently activated microglia associated with the removal of compact amyloid deposits and elevated plasma A[beta], suggesting a peripheral mechanism contributes to removal of brain A[beta].
Thesis (Ph.D.)--University of South Florida, 2004.
Includes bibliographical references.
Text (Electronic thesis) in PDF format.
System requirements: World Wide Web browser and PDF reader.
Mode of access: World Wide Web.
ABSTRACT: Alzheimers disease (AD) is defined as a progressive neurodegenerative disorder that gradually destroys a persons memory and ability to learn. There are three pathological hallmarks of the disease which are necessary for diagnosis of AD, these are; extracellular amyloid plaques composed of [beta]-amyloid (A[beta]) protein, intracellular neurofibrillary tangles and neuronal loss. Amyloid plaques exist as both compact deposits which stain with Congo red and more numerous diffuse deposits. Active immunization against A[beta] 1-42 or passive immunization with monoclonal anti-A[beta] antibodies reduces amyloid deposition and improves cognition in APP transgenic mice.Over several studies of active immunization in APP+PS1 transgenic mice we showed a strong correlation between reduction of compact amyloid deposits and the degree of microglial activation suggesting a potential role of microglia in the removal of A[beta].
Injection of anti-A[beta] antibodies into the frontal cortex and hippocampus of aged APP transgenic mice revealed an early phase of A[beta] removal which was removal of only diffuse amyloid deposits with no associated activation of microglia. A later phase was the removal of compact amyloid deposits. This was associated with significant activation of microglia. Prevention of this microglial activation by anti-A[beta] F(ab)2 fragments or its inhibition by dexamethasone also precluded the removal of compact amyloid deposits but did not affect the removal of the diffuse deposits. Systemic injection of anti-A[beta] antibodies weekly over a period of 1, 2, 3 and 5 months transiently activated microglia associated with the removal of compact amyloid deposits and elevated plasma A[beta], suggesting a peripheral mechanism contributes to removal of brain A[beta].
Adviser: David Morgan Ph.D.
Immunization.
Transgenic mice.
Inflammation.
Alzheimers disease.