Aβ42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology

Rebecca Radde, Tristan Bolmont, Stephan A. Kaeser, Janaky Coomaraswamy, Dennis Lindau, Lars Stoltze, Michael E. Calhoun, Fabienne Jäggi, Hartwig Wolburg, Simon Gengler, Christian Haass, Bernardino Ghetti, Christian Czech, Christian Hölscher, Paul M. Mathews, Mathias Jucker

Research output: Contribution to journalArticle

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Abstract

We have generated a novel transgenic mouse model on a C57BL/6J genetic background that coexpresses KM670/671NL mutated amyloid precursor protein and L166P mutated presenilin 1 under the control of a neuron-specific Thy1 promoter element (APPPS1 mice). Cerebral amyloidosis starts at 6-8 weeks and the ratio of human amyloid (A)β42 to Aβ40 is 1.5 and 5 in pre-depositing and amyloid-depositing mice, respectively. Consistent with this ratio, extensive congophilic parenchymal amyloid but minimal amyloid angiopathy is observed. Amyloid-associated pathologies include dystrophic synaptic boutons, hyperphosphorylated tau-positive neuritic structures and robust gliosis, with neocortical microglia number increasing threefold from 1 to 8 months of age. Global neocortical neuron loss is not apparent up to 8 months of age, but local neuron loss in the dentate gyrus is observed. Because of the early onset of amyloid lesions, the defined genetic background of the model and the facile breeding characteristics, APPPS1 mice are well suited for studying therapeutic strategies and the pathomechanism of amyloidosis by cross-breeding to other genetically engineered mouse models.

Original languageEnglish
Pages (from-to)940-946
Number of pages7
JournalEMBO Reports
Volume7
Issue number9
DOIs
StatePublished - Sep 2006

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Pathology
Amyloid
Transgenic Mice
Neurons
Breeding
Presenilin-1
Gliosis
Amyloid beta-Protein Precursor
Genetic Models
Dentate Gyrus
Presynaptic Terminals
Microglia
Amyloidosis
Amyloid angiopathy
Genetic Background

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Radde, R., Bolmont, T., Kaeser, S. A., Coomaraswamy, J., Lindau, D., Stoltze, L., ... Jucker, M. (2006). Aβ42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology. EMBO Reports, 7(9), 940-946. https://doi.org/10.1038/sj.embor.7400784

Aβ42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology. / Radde, Rebecca; Bolmont, Tristan; Kaeser, Stephan A.; Coomaraswamy, Janaky; Lindau, Dennis; Stoltze, Lars; Calhoun, Michael E.; Jäggi, Fabienne; Wolburg, Hartwig; Gengler, Simon; Haass, Christian; Ghetti, Bernardino; Czech, Christian; Hölscher, Christian; Mathews, Paul M.; Jucker, Mathias.

In: EMBO Reports, Vol. 7, No. 9, 09.2006, p. 940-946.

Research output: Contribution to journalArticle

Radde, R, Bolmont, T, Kaeser, SA, Coomaraswamy, J, Lindau, D, Stoltze, L, Calhoun, ME, Jäggi, F, Wolburg, H, Gengler, S, Haass, C, Ghetti, B, Czech, C, Hölscher, C, Mathews, PM & Jucker, M 2006, 'Aβ42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology', EMBO Reports, vol. 7, no. 9, pp. 940-946. https://doi.org/10.1038/sj.embor.7400784
Radde R, Bolmont T, Kaeser SA, Coomaraswamy J, Lindau D, Stoltze L et al. Aβ42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology. EMBO Reports. 2006 Sep;7(9):940-946. https://doi.org/10.1038/sj.embor.7400784
Radde, Rebecca ; Bolmont, Tristan ; Kaeser, Stephan A. ; Coomaraswamy, Janaky ; Lindau, Dennis ; Stoltze, Lars ; Calhoun, Michael E. ; Jäggi, Fabienne ; Wolburg, Hartwig ; Gengler, Simon ; Haass, Christian ; Ghetti, Bernardino ; Czech, Christian ; Hölscher, Christian ; Mathews, Paul M. ; Jucker, Mathias. / Aβ42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology. In: EMBO Reports. 2006 ; Vol. 7, No. 9. pp. 940-946.
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