The DOI matches its Crossref record; 51 of the 52 references it cites were found in a registry or an index.
Aβ peptide immunization restores blood‐brain barrier integrity in Alzheimer disease
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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“impairments of the BBB have been observed in this context (Dickstein et al., 2006; Zipser et al., 2007; Lassman et al., 2012; Figure 2).”
From The impact of microglial activation on blood-brain barrier in brain diseases (2014) · cites this paper as Dickstein et al., 2006
In the citing paper
“It has already been shown that the elimination of Aβ from the brain and the consequent impairment of microglial activation decrease ROS, nitrogen compounds and also inflammatory cytokines produced by microglial cells, which are correlated with the activation of ECs (Dickstein et al., 2006).”
From The impact of microglial activation on blood-brain barrier in brain diseases (2014) · cites this paper as Dickstein et al., 2006
Citations
Cites
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F4/80, a monoclonal antibody directed specifically against the mouse macrophage
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Aβ peptide vaccination prevents memory loss in an animal model of Alzheimer's disease
Morgan, D., Diamond, D. M., Gottschall, P. E., Ugen, K. E., Dickey, C. A., Hardy, J., Duff, K., Jantzen, P. T., DiCarlo, G., Wilcock, D. M., et al. (2000) · Nature · doi:10.1038/35050116 · Cited by 1,506
Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease
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Dysfunction of the neurovascular unit as a temporal driver in Alzheimer’s pathogenesis
Wang, L., Han, L., & Liu, S. (2026) · Translational Neurodegeneration · doi:10.1186/s40035-026-00548-2 · Cited by 6
“Aβ immunization has been shown to restore BBB integrity in AD models, demonstrating that targeting Aβ can repair vascular function [13].”
Deciphering the focal role of endostatin in Alzheimer’s disease
Kaur, D., Behl, T., Chigurupati, S., Sehgal, A., Singh, S., Sharma, N., Badavath, V. N., Vargas-De-La-Cruz, C. B., Bhatia, S., Al‐Harrasi, A., et al. (2021) · Environmental Science and Pollution Research · doi:10.1007/s11356-021-16567-7 · Cited by 4
“2003) and impaired CBF (hypoperfusion) (Dickstein et al. 2006).”
BackgroundMultifunctional Effects of Human Serum Albumin Toward Neuroprotection in Alzheimer Disease
Ezra, A., Rabinovich-Nikitin, I., Rabinovich‐Toidman, P., & Solomon, B. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-803690-7.00011-9 · Cited by 6
Werner, C., Mathkour, M., & Tubbs, R. S. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-819509-3.00014-6 · Cited by 3
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“AD murine models before the appearance of other disease pathology [57, 58].”
BackgroundGenomic and proteomic conversion of brain ischemia to Alzheimer’s disease
Pluta, R. M., & Ułamek-Kozioł, M. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1804251 · Cited by 3
Vascular endothelial growth factor and regional cerebral blood flow in early Alzheimer’s disease
Song, B. X., Jiang, G., Wong, M., Gallagher, D., MacIntosh, B. J., Andreazza, A. C., Beroncal, E. L., Black, S. E., Herrmann, N., Charles, J., et al. (2025) · Journal of Neurophysiology · doi:10.1152/jn.00604.2024 · Cited by 2
Fibrin Formation and Dissolution in the Progression of Amyloid-Beta Pathology in Alzheimer's Disease
Paul, J. (2025) · Digital Commons - RU (Rockefeller University) · doi:10.48496/m50g-qv97
Response to “The pattern of drug delivery really matters”
Zhang, S., & Chen, Z. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.05.006
The Future Role of Biomarkers in Alzheimer’s Disease Diagnostics
Richens, J. L., Vafadar-Isfahani, B., Vere, K., Ball, G., Kalsheker, N. A., Rees, R. C., Bajaj, N. P. S., O’Shea, P., & Morgan, K. (2013) · Springer eBooks · doi:10.1007/978-1-4614-7309-1_13
Zhu, Y., Jafari, Z., Kolb, B. E., & Mohajerani, M. H. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.107004
Metadata
- Authors
- Dickstein, D. L., Biron, K. E., Ujiie, M., Pfeifer, C. G., Jeffries, A. R., & Jefferies, W. A.
- Affiliations
- University of British Columbia (CA)
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2006-03
- Volume
- 20
- Issue
- 3
- Pages
- 426-433
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- 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
- 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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