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Neurodegeneration in an Animal Model of Chronic Amyloid-beta Oligomer Infusion Is Counteracted by Antibody Treatment Infused with Osmotic Pumps
Published on: August 14, 2016
Abeta species removal after abeta42 immunization
James A R Nicoll1, Edward Barton, Delphine Boche
1Division of Clinical Neurosciences, School of Medicine, University of Southampton, Southampton, UK.
Journal of Neuropathology and Experimental Neurology
|November 7, 2006
Summary
Alzheimer disease immunotherapy using amyloid-beta (Abeta) antibodies effectively cleared Abeta plaques in the brain. However, residual tau pathology and cerebral amyloid angiopathy require further investigation for effective treatment.
Area of Science:
- Neuropathology
- Immunotherapy
- Neurodegenerative Diseases
Background:
- Alzheimer disease is characterized by amyloid-beta (Abeta) plaques and tau pathology.
- Previous studies explored Abeta immunotherapy for Alzheimer disease treatment.
Purpose of the Study:
- To neuropathologically assess the effects of Abeta immunotherapy in Alzheimer disease patients.
- To evaluate the clearance of different Abeta species and associated pathologies.
Main Methods:
- Neuropathologic examination of brain tissue from 3 Alzheimer disease patients post-immunotherapy.
- Immunohistochemistry using antibodies specific for various Abeta species and tau pathology markers.
Main Results:
- Evidence of active plaque clearance with "moth-eaten" plaques and microglial phagocytosis of Abeta observed.
- Extensive plaque clearance (69-86% plaque-free cortex) noted in 2 out of 3 cases within 1-2 years.
- Clearance of all major Abeta species (Abeta40, Abeta42, N-terminal truncated Abeta) confirmed.
- Resolution of tau-containing dystrophic neurites, but persistence of tangles, neuropil threads, and cerebral amyloid angiopathy.
Conclusions:
- Abeta immunotherapy can effectively clear various Abeta species from the cerebral cortex.
- Residual tau pathology and cerebral amyloid angiopathy remain significant challenges for Alzheimer disease treatment.
- Further research is needed to address persistent pathologies for therapeutic application of Abeta immunotherapy.
