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Aβ peptide immunization restores blood‐brain barrier integrity in Alzheimer disease
Author(s) -
Dickstein Dara L.,
Biron Kaan E.,
Ujiie Maki,
Pfeifer Cheryl G.,
Jeffries Andrew R.,
Jefferies Wilfred A.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-3956com
Subject(s) - blood–brain barrier , neuropathology , immune system , immunization , medicine , senile plaques , neuroinflammation , neuroscience , immunology , disease , alzheimer's disease , pathology , central nervous system , biology
Immunization with amyloid beta (Aβ) peptides or passive immunization with antibodies against Aβ 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 Aβ 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 Aβ immunization the immune system clears Aβ from sources in the brain as it would in peripheral organs lacking barriers. Once Aβ 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.— Dickstein, D. L., Biron, K. E., Ujiie, M., Pfeifer, C. G., Jeffries, A. R., Jefferies, W. A. Aβ peptide immunization restores blood‐brain barrier integrity in Alzheimer disease. FASEB J. 20, 426–433 (2006)