Alzheimer’s disease (AD) as an ultimate form of brain aging

西道 隆臣


Essentially all of you will be affected by AD if you live up to 120 years old, indicating that AD is an ultimate form of brain aging. Although the cause-and-effect relationship has been established, the etiological mechanisms remain elusive, indicating that we need relevant animal models. Generation of mouse models that overexpress mutant APP and APP/PS1 resulted in failure of more than 400 candidate medications during the past two decades. We thus created single Appknock-in mice that accumulate Aβ without overexpressing APP. Experiments using the new models indicated that a number of phenotypes observed in the overexpression paradigm are artifacts. In addition, they allowed introduction of protective and pathogenic mutations into App and Psen1 genes, respectively, by genome editing. Right now, our mouse models are being used by more than 320 laboratories all over the world. We are creating a paradigm shift in the AD research.

References: Saito et al. Nat Neurosci (2014); Saito et al. J Neurosci (2016); Sasaguri et al. EMBO J (2017) ; Hashimoto et al. J Biol Chem (2018); Hashimoto et al. Open Biol Royal Soc (2018); Nagata et al. Nat Comm (2018); Sasaguri et al. Nat Comm (2018)