APP mouse models for Alzheimer's disease preclinical studies

EMBO J. 2017 Sep 1;36(17):2473-2487. doi: 10.15252/embj.201797397. Epub 2017 Aug 1.


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.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease*
  • Amyloid beta-Protein Precursor / genetics*
  • Animals
  • Disease Models, Animal*
  • Humans


  • Amyloid beta-Protein Precursor