Cited by 111Alzheimer's disease research and treatmentsBarrier Structure and Function StudiesNeuroinflammation and Neurodegeneration Mechanisms

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Aβ peptide immunization restores blood‐brain barrier integrity in Alzheimer disease

Dickstein, Dara L., Biron, Kaan E., Ujiie, Maki, Pfeifer, Cheryl G., Jeffries, Andrew R., Jefferies, Wilfred A.·2006·The FASEB Journal

DOI 10.1096/fj.05-3956com

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Abstract

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.

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Authors: Dickstein, D. L., Biron, K. E., Ujiie, M., Pfeifer, C. G., Jeffries, A. R., & Jefferies, W. A.
Affiliations: University of British Columbia (CA)
ORCID: Dickstein, Dara L.
Pfeifer, Cheryl G.
Jefferies, Wilfred A.
Venue: The FASEB Journal
Publisher: Wiley
Published: 2006-03
Volume: 20
Issue: 3
Pages: 426-433
ISSN: 0892-6638 (ISSN-L)
1530-6860
DOI: 10.1096/fj.05-3956com
OpenAlex: W2021255508
Cited by: 111
References: 52
Citations by year: 2026: 3 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 5 · 2021: 6 · 2020: 3 · 2019: 5 · 2018: 2 · 2017: 4 · 2016: 3 · 2015: 8 · 2014: 9 · 2013: 5 · 2012: 4
FWCI: 7.29
Type: journal article
Language: en
Update notices: erratum (2006-07-01)
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: The FASEB Journal (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: amyloid-beta immunization, blood-brain barrier integrity, Alzheimer's disease, Tg2576 mice, blood-brain barrier permeability, amyloid plaque clearance, microglial activation, amyloid pathology, neuroinflammation
MeSH terms: Alzheimer Disease, Animals, Antibodies, Blood-Brain Barrier, Disease Models, Animal, Female, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Organ Specificity, Peptide Fragments, Vaccination, Amyloid beta-Peptides, Microglia, Mice, Plaque, Amyloid

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Aβ peptide immunization restores blood‐brain barrier integrity in Alzheimer disease

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