Abeta peptide immunization restores blood-brain barrier integrity in Alzheimer disease

Immunization with amyloid beta (Abeta) peptides or passive immunization with antibodies against Abeta has been reported to reduce plaque burden, neuritic dystrophy, early Tau pathology, microgliosis as well as reversing learning and memory deficits. This has created a central paradox: how does vacci...

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Bibliographic Details
Published in:The FASEB journal 2006-03, Vol.20 (3), p.426-433
Main Authors: Dickstein, Dara L, Biron, Kaan E, Ujiie, Maki, Pfeifer, Cheryl G, Jeffries, Andrew R, Jefferies, Wilfred A
Format: Article
Language:English
Subjects:
Alzheimer Disease - immunology
Alzheimer Disease - pathology
Alzheimer Disease - physiopathology
Alzheimer Disease - therapy
Amyloid beta-Peptides - immunology
Animals
Antibodies - immunology
Antibodies - metabolism
Blood-Brain Barrier
Disease Models, Animal
Female
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microglia - immunology
Organ Specificity
Peptide Fragments - immunology
Plaque, Amyloid - immunology
Vaccination
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Summary:Immunization with amyloid beta (Abeta) peptides or passive immunization with antibodies against Abeta has been reported to reduce plaque burden, neuritic dystrophy, early Tau pathology, microgliosis as well as reversing learning and memory deficits. This has created a central paradox: how does vaccination in peripheral tissues reduce plaque burden in the brain? No single explanation for these phenomena has yet been presented. To reconcile these observations, we demonstrate that the integrity of the blood-brain barrier (BBB), a structural barrier between the brain and the blood, is compromised in Tg2576 Alzheimer disease (AD) model mice. We immunized Tg2576 mice with Abeta before and after the onset of AD-type neuropathology and observed that BBB permeability, amyloid burden, and microgliosis are decreased in immunized mice. It is concluded that the integrity of the BBB is disrupted in AD mice, and after Abeta immunization the immune system clears Abeta from sources in the brain as it would in peripheral organs lacking barriers. Once Abeta is removed, the integrity of the BBB is restored. The data therefore provide an intellectual framework for understanding how the immune system can clear amyloid deposits from AD brains and suggest new strategies for limiting disease progression in amyloidopathies.
ISSN:1530-6860