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Capillary cerebral amyloid angiopathy is associated with vessel occlusion and cerebral blood flow disturbances
Abstract
The role of cerebral amyloid angiopathy (CAA) in the pathogenesis of Alzheimer's disease (AD) is not fully understood. Here, we studied whether CAA is associated with alterations in microvascularisation in transgenic mouse models and in the human brain. APP23 mice at 25-26 months of age exhibited severe CAA in thalamic vessels whereas APP51/16 mice did not. Wild-type littermates were free of CAA. We found CAA-related capillary occlusion within the thalamus of APP23 mice but not in APP51/16 and wild-type mice. Magnetic resonance angiography (MRA) showed blood flow alterations in the thalamic vessels of APP23 mice. CAA-related capillary occlusion in the branches of the thalamoperforating arteries of APP23 mice, thereby, corresponded to the occurrence of blood flow disturbances. Similarly, CAA-related capillary occlusion was observed in the human occipital cortex of AD cases but less frequently in controls. These results indicate that capillary CAA can result in capillary occlusion and is associated with cerebral blood flow disturbances providing an additional mechanism for toxic effects of the amyloid beta-protein in AD.
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“VAβ is detrimental to the function of cerebrovascular circulation through compromising blood–brain-barrier integrity [49], effecting hemodynamic dysfunction [29, 50], and facilitating occurrence of spontaneous hemorrhages [25, 26, 36].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [29]
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Metadata
- Authors
- Thal, D. R., Capetillo-Zarate, E., Larionov, S., Staufenbiel, M., Zurbruegg, S., & Beckmann, N.
- Affiliations
- University of Bonn (DE)
- Novartis (Switzerland) (CH)
- Corresponding author
- Thal, Dietmar Rudolf
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 30
- Issue
- 12
- Pages
- 1936-1948
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W1994609866
- Cited by
- 138
- References
- 67
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 3 · 2022: 13 · 2021: 14 · 2020: 5 · 2019: 6 · 2018: 6 · 2017: 6 · 2016: 9 · 2015: 7 · 2014: 8 · 2013: 9 · 2012: 10
- FWCI
- 6.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chinese Academy of Agricultural Sciences
- Novartis Institutes for BioMedical Research
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- cerebral amyloid angiopathy, capillary occlusion, cerebral blood flow, Alzheimer's disease, APP23 mice, thalamus, amyloid-beta, microvascular dysfunction, occipital cortex, transgenic mouse model
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Animals, Brain, Capillaries, Cerebrovascular Circulation, Disease Models, Animal, Female, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Occipital Lobe, Species Specificity, Thalamus, Cerebral Amyloid Angiopathy, Mice, Microvessels
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