APP mouse models for Alzheimer's disease preclinical studies

Hiroki Sasaguri*, Per Nilsson, Shoko Hashimoto, Kenichi Nagata, Takashi Saito, Bart De Strooper, John Hardy, Robert Vassar, Bengt Winblad, Takaomi C. Saido

*Corresponding author for this work

Research output: Contribution to journalReview article

159 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2473-2487
Number of pages15
JournalEMBO Journal
Volume36
Issue number17
DOIs
StatePublished - Sep 1 2017

Keywords

  • APP transgenic
  • Alzheimer's disease
  • App knock-in
  • amyloid precursor protein
  • amyloid β peptide

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Sasaguri, H., Nilsson, P., Hashimoto, S., Nagata, K., Saito, T., De Strooper, B., Hardy, J., Vassar, R., Winblad, B., & Saido, T. C. (2017). APP mouse models for Alzheimer's disease preclinical studies. EMBO Journal, 36(17), 2473-2487. https://doi.org/10.15252/embj.201797397