@article{b1cdebbe4dd84d4da4e1219952373c2c,
title = "APP mouse models for Alzheimer's disease preclinical studies",
abstract = "Animal models of human diseases that accurately recapitulate clinical pathology are indispensable for understanding molecular mechanisms and advancing preclinical studies. The Alzheimer's disease (AD) research community has historically used first-generation transgenic (Tg) mouse models that overexpress proteins linked to familial AD (FAD), mutant amyloid precursor protein (APP), or APP and presenilin (PS). These mice exhibit AD pathology, but the overexpression paradigm may cause additional phenotypes unrelated to AD. Second-generation mouse models contain humanized sequences and clinical mutations in the endogenous mouse App gene. These mice show Aβ accumulation without phenotypes related to overexpression but are not yet a clinical recapitulation of human AD. In this review, we evaluate different APP mouse models of AD, and review recent studies using the second-generation mice. We advise AD researchers to consider the comparative strengths and limitations of each model against the scientific and therapeutic goal of a prospective preclinical study.",
keywords = "APP transgenic, Alzheimer's disease, App knock-in, amyloid precursor protein, amyloid β peptide",
author = "Hiroki Sasaguri and Per Nilsson and Shoko Hashimoto and Kenichi Nagata and Takashi Saito and {De Strooper}, Bart and John Hardy and Robert Vassar and Bengt Winblad and Saido, {Takaomi C.}",
note = "Funding Information: We thank Lennart Mucke, UCSF, for comments on the manuscript, Makoto Higuchi for sharing valuable information, and Charles Yokoyama, RIKEN, for editorial and editing support, respectively. This work was partially supported by a Grant-in-Aid for Young Scientists (B) and Scientific Research (B) from the Japan Ministry of Education, Culture, Sports, Science, and Technology (MEXT) (S.H and T.S.); Special Postdoctoral Researchers Program from RIKEN (K.N. and S.H.); the Japan Science and Technology Agency Precursory Research for Embryonic Science and Technology (T.S.); the Strategic Research Program for Brain Sciences, Japan Agency for Medical Research and Development (AMED) (T.S.), and the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) project of AMED (T.C.S.); Aging Project of RIKEN (T.C.S.), the Swedish Research Council (P.N.), Alzheimerfonden (P.N.), H{\aa}llstens forskningsstiftelse (P.N.), and the National Institutes of Health (R01 AG022560 and R01 AG030142 to R.V.). TCS and TS serve as the CEO and advisor, respectively, for RIKEN BIO Co. Ltd., which sublicenses animal models to for-profit organizations, the profits from which are used for the identification of disease biomarkers. Publisher Copyright: {\textcopyright} 2017 The Authors. Published under the terms of the CC BY 4.0 license",
year = "2017",
month = sep,
day = "1",
doi = "10.15252/embj.201797397",
language = "English (US)",
volume = "36",
pages = "2473--2487",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "17",
}
