Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid
Autor: | Patrick Burgermeister, Martina Stalder, Christine Sturchler-Pierrat, Michael E. Calhoun, Bernd Sommer, Dorothee Abramowski, Mathias Jucker, Matthias Staufenbiel, Markus Tolnay, Karl-Heinz Wiederhold, Amie L. Phinney |
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Rok vydání: | 1999 |
Předmět: |
Male
Pathology medicine.medical_specialty Aging Amyloid BACE1-AS Gene Expression Mice Transgenic Amyloid beta-Protein Precursor Mice mental disorders medicine Amyloid precursor protein Animals Humans Senile plaques Neurons Multidisciplinary biology Neurodegeneration P3 peptide Biological Transport Neurodegenerative Diseases Biological Sciences medicine.disease Biochemistry of Alzheimer's disease Mice Inbred C57BL Cerebral Amyloid Angiopathy Cerebrovascular Disorders Mutagenesis biology.protein Female Cerebral amyloid angiopathy |
Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 96(24) |
ISSN: | 0027-8424 |
Popis: | 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. |
Databáze: | OpenAIRE |
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