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APP mouse models for Alzheimer's disease preclinical studies
Author(s) -
Sasaguri Hiroki,
Nilsson Per,
Hashimoto Shoko,
Nagata Kenichi,
Saito Takashi,
De Strooper Bart,
Hardy John,
Vassar Robert,
Winblad Bengt,
Saido Takaomi C
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201797397
Subject(s) - biology , disease , alzheimer's disease , neuroscience , bioinformatics , pharmacology , medicine
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.