DOI: 10.1073/pnas.96.24.14088. Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid

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

10.1073/pnas.96.24.14088

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

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.

Bibliography

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. (1999). Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid. Proceedings of the National Academy of Sciences, 96(24), 14088â14093.

Authors 11

Michael E. Calhoun (first)
Patrick Burgermeister (additional)
Amie L. Phinney (additional)
Martina Stalder (additional)
Markus Tolnay (additional)
Karl-Heinz Wiederhold (additional)
Dorothee Abramowski (additional)
Christine Sturchler-Pierrat (additional)
Bernd Sommer (additional)
Matthias Staufenbiel (additional)
Mathias Jucker (additional)

References 39 Referenced 331

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10.1038/39321

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:39 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 4:22 p.m.)
Indexed	2 days, 14 hours ago (Sept. 3, 2025, 7:12 a.m.)
Issued	25 years, 9 months ago (Nov. 23, 1999)
Published	25 years, 9 months ago (Nov. 23, 1999)
Published Online	25 years, 9 months ago (Nov. 23, 1999)
Published Print	25 years, 9 months ago (Nov. 23, 1999)

Funders 0

None

BibTeX

@article{Calhoun_1999, title={Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid}, volume={96}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.96.24.14088}, DOI={10.1073/pnas.96.24.14088}, number={24}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Calhoun, Michael E. and Burgermeister, Patrick and Phinney, Amie L. and Stalder, Martina and Tolnay, Markus and Wiederhold, Karl-Heinz and Abramowski, Dorothee and Sturchler-Pierrat, Christine and Sommer, Bernd and Staufenbiel, Matthias and Jucker, Mathias}, year={1999}, month=nov, pages={14088–14093} }

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