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Cited by 410Alzheimer's disease research and treatmentsIntracerebral and Subarachnoid Hemorrhage ResearchNeuroinflammation and Neurodegeneration Mechanisms

Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid

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Calhoun, Michael E., Burgermeister, Patrick, Phinney, Amie L., Stalder, Martina, Tolnay, Markus, Wiederhold, Karl-Heinz, Abramowski, Dorothee, Sturchler-Pierrat, Christine +3 more·1999·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.96.24.14088PMC PMC24195
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Abstract

Transgenic mice that overexpress mutant human amyloid precursor protein (APP) exhibit one hallmark of Alzheimer’s disease pathology, namely the extracellular deposition of amyloid plaques. Here, we describe significant deposition of amyloid β (Aβ) in the cerebral vasculature [cerebral amyloid angiopathy (CAA)] in aging APP23 mice that had striking similarities to that observed in human aging and Alzheimer’s disease. Amyloid deposition occurred preferentially in arterioles and capillaries and within individual vessels showed a wide heterogeneity (ranging from a thin ring of amyloid in the vessel wall to large plaque-like extrusions into the neuropil). CAA was associated with local neuron loss, synaptic abnormalities, microglial activation, and microhemorrhage. Although several factors may contribute to CAA in humans, the neuronal origin of transgenic APP, high levels of Aβ in cerebrospinal fluid, and regional localization of CAA in APP23 mice suggest transport and drainage pathways rather than local production or blood uptake of Aβ as a primary mechanism underlying cerebrovascular amyloid formation. APP23 mice on an App -null background developed a similar degree of both plaques and CAA, providing further evidence that a neuronal source of APP/Aβ is sufficient to induce cerebrovascular amyloid and associated neurodegeneration.

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Crossref · 10.1073/pnas.96.24.14088

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  • Evidence from animal models suggests capillary cerebral amyloid angiopathy is derived from neuronal Aβ, which leads to impaired perivascular clearance, peri-capillary Aβ deposits and ultimately cerebral amyloid angiopathy.

    “The evidence from animal models suggest capillary CAA is derived from neuronal Aβ, which leads to impaired perivascular clearance, peri-capillary Aβ deposits and ultimately CAA [53].”

    From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [53]

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Authors
Calhoun, M. E., Burgermeister, P., Phinney, A. L., Stalder, M., Tolnay, M., Wiederhold, K.-H., Abramowski, D., Sturchler-Pierrat, C., Sommer, B., Staufenbiel, M., & Jucker, M.
Affiliations
  • Novartis (Switzerland) (CH)
  • Department of Neuropathology, Institute for Pathology, University of Basel, CH-4003 Basel, Switzerland; and Novartis Pharma Ltd., Nervous Systems Research, CH-4002 Basel, Switzerland
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1999-11-23
Volume
96
Issue
24
Pages
14088-14093
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.96.24.14088
PMC
PMC24195
OpenAlex
W1983670592
Cited by
410
References
6
Citations by year
2026: 7 · 2025: 8 · 2024: 7 · 2023: 8 · 2022: 14 · 2021: 8 · 2020: 14 · 2019: 4 · 2018: 16 · 2017: 9 · 2016: 10 · 2015: 11 · 2014: 13 · 2013: 9 · 2012: 15
FWCI
12.68
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • 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
amyloid precursor protein, APP23 transgenic mice, cerebral amyloid angiopathy, amyloid-beta deposition, cerebrovascular amyloid, Alzheimer's disease, neuronal overexpression, microhemorrhages, microglial activation, synaptic abnormalities, neuronal loss, cerebrospinal fluid amyloid-beta, aging
MeSH terms
Aging, Animals, Biological Transport, Cerebrovascular Disorders, Female, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Gene Expression, Mutagenesis, Amyloid beta-Protein Precursor, Cerebral Amyloid Angiopathy, Neurodegenerative Diseases, Mice

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