Exacerbation of Cerebral Amyloid Angiopathy-Associated Microhemorrhage in Amyloid Precursor Protein Transgenic Mice by Immunotherapy Is Dependent on Antibody Recognition of Deposited Forms of Amyloid β
Open accessAbstract
Passive immunization with an antibody directed against the N terminus of amyloid beta (Abeta) has recently been reported to exacerbate cerebral amyloid angiopathy (CAA)-related microhemorrhage in a transgenic animal model. Although the mechanism responsible for the deleterious interaction is unclear, a direct binding event may be required. We characterized the binding properties of several monoclonal anti-Abeta antibodies to deposited Abeta in brain parenchyma and CAA. Biochemical analyses demonstrated that the 3D6 and 10D5, two N-terminally directed antibodies, bound with high affinity to deposited forms of Abeta, whereas 266, a central domain antibody, lacked affinity for deposited Abeta. To determine whether 266 or 3D6 would exacerbate CAA-associated microhemorrhage, we treated aged PDAPP mice with either antibody for 6 weeks. We observed an increase in both the incidence and severity of CAA-associated microhemorrhage when PDAPP transgenic mice were treated with the N-terminally directed 3D6 antibody, whereas mice treated with 266 were unaffected. These results may have important implications for future immune-based therapeutic strategies for Alzheimer's disease.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Increased CAA and CAA-associated microhemorrhage are side effects associated with previous passive Aβ immunotherapy, especially with those Aβ antibodies that target aggregated forms of Aβ if the effector function of the antibody is intact.
“Increased CAA and CAA-associated microhemorrhage (Pfeifer et al., 2002;Wilcock et al., 2004a) are side effects associated with previous passive A immunotherapy, especially with those A antibodies that target aggregated forms of A if the effector function of the antibody is intact (Pfeifer et al., 2002;Wilcock et al., 2004a;Racke et al., 2005).”
From Anti-ApoE Antibody Given after Plaque Onset Decreases Aβ Accumulation and Improves Brain Function in a Mouse Model of Aβ Amyloidosis (2014) · cites this paper as Racke et al., 2005
The Introduction and Discussion report that passive treatment with an antibody binding deposited Aβ increased CAA-associated microhemorrhage in aged transgenic mice, while an antibody that did not bind deposits had no such effect. The paper does not establish that intact antibody effector function is required, nor does it show an increase in CAA itself after treatment; its reported increase is in CAA-associated microhemorrhage. (LLM, conf=0.87)
Experimental — accuracy not yet measuredApplication of N-terminus specific mAbs, which like 10D5 bind epitopes exposed in Aβ parenchymal plaques and VAβ, but not mAbs, which like m266 bind the Aβ central domain and do not bind to deposited Aβ, effect increased hemorrhage incidence.
“Thus, application of N-terminus specific mAbs, which like10D5 binds epitopes exposed in Aβ parenchymal plaques and VAβ, but not mAbs, which like m266 bind the Aβ central domain and do not bind to deposited Aβ effect increased hemorrhage incidence [64, 65].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [64]
Exacerbation of VAβ associated microhemorrhages appears to be associated with propensity of anti-Aβ mAb to bind deposited Aβ.
“Exacerbation of VAβ associated microhemorrhages appears to be associated with propensity of anti-Aβ mAb to bind deposited Aβ.”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [64]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 46 · Cited by 320
Research works printed but not linked: 1
- Vinters HV (1987) Cerebral amyloid angiopathy: a critical review. Stroke 18:311-324.
- Authors
- Racke, M. M., Boone, L. I., Hepburn, D. L., Parsadainian, M., Bryan, M. T., Ness, D. K., Piroozi, K. S., Jordan, W. H., Brown, D. D., Hoffman, W. P., Holtzman, D. M., Bales, K. R., Gitter, B. D., May, P. C., Paul, S. M., & DeMattos, R. B.
- Affiliations
- Eli Lilly (United States) (US)
- Washington University in St. Louis (US)
- Corresponding author
- DeMattos, Ronald B.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2005-01-19
- Volume
- 25
- Issue
- 3
- Pages
- 629-636
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6725332
- OpenAlex
- W2160676126
- Cited by
- 320
- References
- 46
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 18 · 2023: 7 · 2022: 8 · 2021: 9 · 2020: 8 · 2019: 5 · 2018: 4 · 2017: 8 · 2016: 10 · 2015: 14 · 2014: 21 · 2013: 17 · 2012: 21
- FWCI
- 16.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- cerebral amyloid angiopathy, microhemorrhages, amyloid-beta, anti-amyloid beta antibodies, passive immunization, monoclonal antibodies
- MeSH terms
- Aging, Animals, Antibody Affinity, Cerebral Hemorrhage, Female, Immunization, Passive, Male, Mice, Transgenic, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Cerebral Amyloid Angiopathy, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
