Approach

Summary

Licensing status

Publication and contact information

Disease models

Single amyloid precursor protein (APP) knock-in mouse models of Alzheimer's disease (AD)

Mice that express humanized APP with various knock-in mutations could be useful as models for studying AD pathophysiology and evaluating therapies. The mice were engineered to express humanized APP with knock-in mutations called Swedish, Beyreuther/Iberian or Arctic. Mice with Swedish and Beyreuther mutations showed high levels of b-amyloid 42 (Ab42) compared with mice that had Swedish mutations alone or no mutation and showed Ab deposits at 6 months and memory impairments at 18 months. Mice with all three knock-in mutations had levels of Ab42 and Ab deposits similar to those in mice with Swedish and Beyreuther mutations alone but also showed subcortical amyloidosis, higher levels of microgliosis and astrocytosis and more rapid onset of memory impairments, which parallels disease pathophysiology seen in patients carrying the Arctic mutation. Next steps include using the mice to identify molecular targets to stop or decelerate Ab deposition in the brain for early prevention of AD and creating similar nonhuman primate AD models.

SciBX 7(18); doi:10.1038/scibx.2014.540
Published online May 8, 2014

The APP knock-in mouse model containing the Beyreuther/Iberian mutation is patented; available for nonexclusive licensing from the RIKEN Technology Transfer Office
Contact: Ryosuke Furubayashi, RIKEN Brain Science Institute, Saitama, Japan
e-mail:

ryosuke.furubayashi@riken.jp

Saito, T. et al. Nat. Neurosci.; published online April 13, 2014;
doi:10.1038/nn.3697
Contact: Takaomi C. Saido, RIKEN Brain Science Institute, Saitama, Japan
e-mail:

saido@brain.riken.jp