Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology

• Christine Sturchler-Pierrat

  Novartis Pharma, Inc., S-386.809, CH-4002 Basel, Switzerland; and Institute for Pathology, University of Basel, CH-4003 Basel, Switzerland

• Dorothee Abramowski

  Novartis Pharma, Inc., S-386.809, CH-4002 Basel, Switzerland; and Institute for Pathology, University of Basel, CH-4003 Basel, Switzerland

• Mairead Duke

  Novartis Pharma, Inc., S-386.809, CH-4002 Basel, Switzerland; and Institute for Pathology, University of Basel, CH-4003 Basel, Switzerland

• Karl-Heinz Wiederhold

  Novartis Pharma, Inc., S-386.809, CH-4002 Basel, Switzerland; and Institute for Pathology, University of Basel, CH-4003 Basel, Switzerland

• Claudia Mistl

  Novartis Pharma, Inc., S-386.809, CH-4002 Basel, Switzerland; and Institute for Pathology, University of Basel, CH-4003 Basel, Switzerland

• Sabin Rothacher

  Novartis Pharma, Inc., S-386.809, CH-4002 Basel, Switzerland; and Institute for Pathology, University of Basel, CH-4003 Basel, Switzerland

• Birgit Ledermann

  Novartis Pharma, Inc., S-386.809, CH-4002 Basel, Switzerland; and Institute for Pathology, University of Basel, CH-4003 Basel, Switzerland

• Kurt Bürki

  Novartis Pharma, Inc., S-386.809, CH-4002 Basel, Switzerland; and Institute for Pathology, University of Basel, CH-4003 Basel, Switzerland

• Peter Frey

  Novartis Pharma, Inc., S-386.809, CH-4002 Basel, Switzerland; and Institute for Pathology, University of Basel, CH-4003 Basel, Switzerland

• Paolo A. Paganetti

  Novartis Pharma, Inc., S-386.809, CH-4002 Basel, Switzerland; and Institute for Pathology, University of Basel, CH-4003 Basel, Switzerland

• Caroline Waridel

  Novartis Pharma, Inc., S-386.809, CH-4002 Basel, Switzerland; and Institute for Pathology, University of Basel, CH-4003 Basel, Switzerland

• Michael E. Calhoun

  Novartis Pharma, Inc., S-386.809, CH-4002 Basel, Switzerland; and Institute for Pathology, University of Basel, CH-4003 Basel, Switzerland

• Mathias Jucker

  Novartis Pharma, Inc., S-386.809, CH-4002 Basel, Switzerland; and Institute for Pathology, University of Basel, CH-4003 Basel, Switzerland

• Alphonse Probst

  Novartis Pharma, Inc., S-386.809, CH-4002 Basel, Switzerland; and Institute for Pathology, University of Basel, CH-4003 Basel, Switzerland

• Matthias Staufenbiel

  Novartis Pharma, Inc., S-386.809, CH-4002 Basel, Switzerland; and Institute for Pathology, University of Basel, CH-4003 Basel, Switzerland

• Bernd Sommer

  Novartis Pharma, Inc., S-386.809, CH-4002 Basel, Switzerland; and Institute for Pathology, University of Basel, CH-4003 Basel, Switzerland

抄録

Mutations in the amyloid precursor protein (APP) gene cause early-onset familial Alzheimer disease (AD) by affecting the formation of the amyloid β (Aβ) peptide, the major constituent of AD plaques. We expressed human APP 751 containing these mutations in the brains of transgenic mice. Two transgenic mouse lines develop pathological features reminiscent of AD. The degree of pathology depends on expression levels and specific mutations. A 2-fold overexpression of human APP with the Swedish double mutation at positions 670/671 combined with the V717I mutation causes Aβ deposition in neocortex and hippocampus of 18-month-old transgenic mice. The deposits are mostly of the diffuse type; however, some congophilic plaques can be detected. In mice with 7-fold overexpression of human APP harboring the Swedish mutation alone, typical plaques appear at 6 months, which increase with age and are Congo Red-positive at first detection. These congophilic plaques are accompanied by neuritic changes and dystrophic cholinergic fibers. Furthermore, inflammatory processes indicated by a massive glial reaction are apparent. Most notably, plaques are immunoreactive for hyperphosphorylated tau, reminiscent of early tau pathology. The immunoreactivity is exclusively found in congophilic senile plaques of both lines. In the higher expressing line, elevated tau phosphorylation can be demonstrated biochemically in 6-month-old animals and increases with age. These mice resemble major features of AD pathology and suggest a central role of Aβ in the pathogenesis of the disease.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 94 (24), 13287-13292, 1997-11-25

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1363670320021117184
• NII論文ID: 80010032830
• DOI: 10.1073/pnas.94.24.13287
• ISSN: 10916490
• ISSN: 00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.94.24.13287
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