Thursday, May 8, 2014
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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
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
Contact: Ryosuke Furubayashi, RIKEN Brain Science Institute,
Saito, T. et al. Nat.
Neurosci.; published online April 13, 2014;
Contact: Takaomi C. Saido, RIKEN Brain Science Institute, Saitama,
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