APP mouse models for Alzheimer's disease preclinical studies

• Hiroki Sasaguri ^[4] ; Per Nilsson ^[1] ; Shoko Hashimoto ^[1] ; Kenichi Nagata ^[1] ; Takashi Saito ^[1] ; Bart De Strooper ^[2] ; John Hardy ^[2] ; Robert Vassar ^[3] ; Bengt Winblad ^[5] ; Takaomi C Saido ^[1]
  1. [1] RIKEN Brain Science Institute

     RIKEN Brain Science Institute

     Japón

     
  2. [2] University College London

     University College London

     Reino Unido

     
  3. [3] Northwestern University

     Northwestern University

     Township of Evanston, Estados Unidos

     
  4. [4] 1 Laboratory for Proteolytic Neuroscience RIKEN Brain Science Institute Wako Japan; 2 Department of Neurology and Neurological Science Graduate School of Medicine Tokyo Medical and Dental University Tokyo Japan
  5. [5] 3 Division of Neurogeriatrics Department of Neurobiology, Care Sciences and Society Center for Alzheimer Research Karolinska Institutet Huddinge Sweden

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 36, Nº. 17, 2017, págs. 2473-2487
• Idioma: inglés
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• Resumen

  • 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.