The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Insights into the mechanisms of action of anti‐Aβ antibodies in Alzheimer's disease mouse models
Abstract
A number of hypotheses regarding how anti‐Aβ antibodies alter amyloid deposition have been postulated, yet there is no consensus as to how Aβ immunotherapy works. We have examined the in vivo binding properties, pharmacokinetics, brain penetrance, and alterations in Aβ levels after a single peripheral dose of anti‐Aβ antibodies to both wild‐type (WT) and young non‐Aβ depositing APP and BRI‐Aβ42 mice. The rapid rise in plasma Aβ observed after antibody (Ab) administration is attributable to prolongation of the half‐life of Aβ bound to the Ab. Only a miniscule fraction of Ab enters the brain, and despite dramatic increases in plasma Aβ, we find no evidence that total brain Aβ levels are significantly altered. Surprisingly, cerebral spinal fluid Aβ levels transiently rise, and when Ab:Aβ complex is directly injected into the lateral ventricles of mice, it is rapidly cleared from the brain into the plasma where it remains stable. When viewed in context of daily turnover of Aβ, these data provide a framework to evaluate proposed mechanisms of Aβ attenuation mediated by peripheral administration of an anti‐Aβ monoclonal antibody (mAb) effective in passive immunization paradigm. Such quantitative data suggest that the mAbs are either indirectly enhancing clearance of Aβ or targeting a low abundance aggregation intermediate.—Levites, Y., Smithson, L. A., Price, R. W., Dakin. R. S., Yuan, B., Sierks, M. R., Kim, J., McGowan, E., Reed, D. K., Rosenberry, T. L., Das, P., Golde, T. E. Insights into the mechanisms of action of anti‐Aβ antibodies in Alzheimer's disease mouse models. FASEB J. 20, E2002–E2014 (2006)
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Metadata
- Authors
- Levites, Y., Smithson, L. A., Price, R. W., Dakin, R. S., Yuan, B., Sierks, M. R., Kim, J., McGowan, E., Kim Reed, D., Rosenberry, T. L., Das, P., Golde, T. E., Levites, Y., Smithson, L. A., Price, R. W., Dakin, R. S., Yuan, B., Sierks, M. R., Kim, J., McGowan, E., Kim Reed, D., Rosenberry, T. L., Das, P., & Golde, T. E.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2006-10-26
- Volume
- 20
- Issue
- 14
- Pages
- 2576-2578
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2091723502
- Semantic Scholar
- 97676444e5cdee032b67a599961944ce98e967f9
- Cited by
- 113
- References
- 60
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 3 · 2022: 6 · 2021: 3 · 2020: 7 · 2019: 3 · 2018: 8 · 2017: 8 · 2016: 4 · 2015: 8 · 2014: 10 · 2013: 8 · 2012: 7
- FWCI
- 4.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Funders
- Mayo Foundation for Medical Education and Research
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- anti-amyloid beta antibodies, Alzheimer's disease, amyloid-beta immunotherapy, passive immunization, amyloid-beta clearance, pharmacokinetics, brain penetration, APP transgenic mice
- MeSH terms
- Alzheimer Disease, Animals, Antibodies, Monoclonal, Brain, Disease Models, Animal, Female, Immunization, Passive, Mice, Transgenic, Amyloid beta-Peptides, Mice
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