Vascular alterations in PDAPP mice after anti‐Aβ immunotherapy: Implications for amyloid‐related imaging abnormalities
Abstract
Background Clinical studies of β-amyloid (Aβ) immunotherapy in Alzheimer's disease (AD) patients have demonstrated reduction of central Aβ plaque by positron emission tomography (PET) imaging and the appearance of amyloid-related imaging abnormalities (ARIA). To better understand the relationship between ARIA and the pathophysiology of AD, we undertook a series of studies in PDAPP mice evaluating vascular alterations in the context of central Aβ pathology and after anti-Aβ immunotherapy. Methods We analyzed PDAPP mice treated with either 3 mg/kg/week of 3D6, the murine form of bapineuzumab, or isotype control antibodies for periods ranging from 1 to 36 weeks and evaluated the vascular alterations in the context of Aβ pathology and after anti-Aβ immunotherapy. The number of mice in each treatment group ranged from 26 to 39 and a total of 345 animals were analyzed. Results The central vasculature displayed morphological abnormalities associated with vascular Aβ deposits. Treatment with 3D6 antibody induced clearance of vascular Aβ that was spatially and temporally associated with a transient increase in microhemorrhage and in capillary Aβ deposition. Microhemorrhage resolved over a time period that was associated with a recovery of vascular morphology and a decrease in capillary Aβ accumulation. Conclusions These data suggest that vascular leakage events, such as microhemorrhage, may be related to the removal of vascular Aβ. With continued treatment, this initial susceptibility…
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Time course analysis of VAβ-related events during immunotherapy in PDAPP mice revealed that a time window for increased incidence of microhemorrhages can last up to six months, but then their incidence diminishes drastically, which correlates with achieving significant clearance of both CAA and CCA.
“Time course analysis of VAβ-related events during immunotherapy in PDAPP mice, revealed that a time window for increased incidence of microhemorrhages can last up to six months, but then their incidence diminishes drastically, which correlates with achieving significant clearance of both CAA and CCA [21].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [21]
Aβ immunotherapy can ameliorate VAβ burden and improve compromised vascular reactivity.
“Aβ immunotherapy can ameliorate VAβ burden and improve compromised vascular reactivity [12, 21, 63], but it is well known to escalate incidence of brain microhemorrhages [21, 26].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [21]
Aβ immunotherapy is well known to escalate incidence of brain microhemorrhages.
“Aβ immunotherapy can ameliorate VAβ burden and improve compromised vascular reactivity [12, 21, 63], but it is well known to escalate incidence of brain microhemorrhages [21, 26].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [21]
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BackgroundMethodInfluential
- Authors
- Zago, W., Schroeter, S., Guido, T., Khan, K., Seubert, P., Yednock, T., Schenk, D., Gregg, K. M., Games, D., Bard, F., & Kinney, G. G.
- Affiliations
- Janssen Alzheimer Immunotherapy Research & Development (United States) (US)
- Corresponding author
- Kinney, Gene G.
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2013-04-15
- Volume
- 9
- Issue
- 5S
- Pages
- S105-15
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- OpenAlex
- W2120520848
- Cited by
- 75
- References
- 9
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 6 · 2023: 7 · 2022: 6 · 2021: 7 · 2019: 3 · 2018: 4 · 2017: 8 · 2016: 8 · 2015: 5 · 2014: 5 · 2013: 2
- FWCI
- 4.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Alzheimer s & Dementia (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- School of Medicine, Emory University
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- amyloid-related imaging abnormalities, anti-amyloid immunotherapy
- MeSH terms
- Alzheimer Disease, Animals, Blood Vessels, Brain, Disease Models, Animal, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Meninges, Mice, Transgenic, Mutation, Time Factors, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Intracranial Hemorrhages, Collagen Type IV, Microscopy, Electron, Transmission, Mice, Aquaporin 4, Antibodies, Monoclonal, Humanized
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