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

APP mouse models for Alzheimer's disease preclinical studies.

Author information

1
Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako, Japan hiroki.sasaguri@riken.jp saido@brain.riken.jp.
2
Department of Neurology and Neurological Science, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
3
Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako, Japan.
4
Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Huddinge, Sweden.
5
Department of Neuroscience and Pathobiology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
6
Dementia Research Institute, University College London, London, UK.
7
Department for Neurosciences, KU Leuven, Leuven, Belgium.
8
VIB Center for Brain and Disease Research, Leuven, Belgium.
9
Reta Lila Research Laboratories and the Department of Molecular Neuroscience, University College London Institute of Neurology, London, UK.
10
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

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

PMID:
28768718
PMCID:
PMC5579350
DOI:
10.15252/embj.201797397
[Indexed for MEDLINE]
Free PMC Article

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