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Altered morphology and 3D architecture of brain vasculature in a mouse model for Alzheimer's disease
Open accessAbstract
Substantial evidence from epidemiological, pathological, and clinical reports suggests that vascular factors are critical in the pathogenesis of Alzheimer's disease (AD), and changes in blood flow are currently the most reliable indicators of the disease. We previously reported that older APP23 transgenic (tg) mice have significant blood flow alterations correlated with structural modifications of blood vessels. For the present study, our objective was to analyze the age-dependent morphological and architectural changes of the cerebral vasculature of APP23 tg mice. To visualize the 3D arrangement of the entire brain vasculature, we used vascular corrosion casts. Already at young ages, when typically parenchymal amyloid plaques are not yet present, APP23 tg mice had significant alterations, particularly of the microvasculature, often accompanied by small deposits attached to the vessels. In older animals, vasculature abruptly ended at amyloid plaques, resulting in holes. Often, small deposits were sitting near or at the end of truncated vessels. Between such holes, the surrounding vascular array appeared more dense and showed features typical for angiogenesis. We propose that small amyloid aggregates associated with the microvasculature lead to morphological and architectural alterations of the vasculature, resulting in altered local blood flow. The characteristic early onset of vascular alterations suggests that imaging blood flow and/or vasculature architecture could be used as a tool for early diagnosis of the disease and to monitor therapies.
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“A number of structural and functional consequences of vasculopathy have been reported in murine models of amyloidosis, such as reduced cortical blood flow already early in life (He ´bert et al., 2013), as well as damaged capillary systems (Meyer et al., 2008).”
From Early Alterations in Functional Connectivity and White Matter Structure in a Transgenic Mouse Model of Cerebral Amyloidosis (2014) · cites this paper as Meyer et al., 2008
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Metadata
- Authors
- Meyer, E. P., Ulmann-Schuler, A., Staufenbiel, M., & Krucker, T.
- Affiliations
- University of Zurich (CH)
- *Department of Zoology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland;
- Novartis Institutes for BioMedical Research (CH)
- Novartis Institutes for BioMedical Research, Inc., Discovery Technologies, Cambridge, MA 02139; and
- Corresponding author
- Krucker, Thomas
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-03-04
- Volume
- 105
- Issue
- 9
- Pages
- 3587-3592
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2265182
- OpenAlex
- W2146417688
- Cited by
- 260
- References
- 60
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 13 · 2023: 15 · 2022: 12 · 2021: 16 · 2020: 18 · 2019: 17 · 2018: 18 · 2017: 17 · 2016: 14 · 2015: 10 · 2014: 16 · 2013: 12 · 2012: 20
- FWCI
- 9.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- Alzheimer's disease, APP23 transgenic mice, cerebral vasculature, microcirculation, amyloid plaques, blood flow, vascular corrosion casts, angiogenesis, early diagnosis, amyloid aggregates
- MeSH terms
- Age Factors, Alzheimer Disease, Animals, Capillaries, Cerebrovascular Circulation, Cerebrovascular Disorders, Mice, Transgenic, Corrosion Casting, Models, Animal, Mice, Plaque, Amyloid
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