![]() This large‐scale failure by the pharmaceutical industry and biomedical research community can be attributed to many factors, including inappropriate choice of mouse models, wrong timing for therapeutic interventions, over‐reliance on inappropriate assays for translational studies, or lack of precise biomarkers, most of which center on efficacy and reproducibility in preclinical studies of which animal models were a critical component. Given the grim epidemiological forecast, scientifically based strategies to prevent AD are urgently needed, as evidenced by the fact that in the previous two decades more than 400 medication candidates failed to reach the clinic (Mangialasche et al, 2010). ![]() In the coming decades, global AD prevalence is projected to reach higher epidemic levels that will place a massive economic burden on society. In 2015, of the ~47 million individuals with dementia worldwide (Prince et al, 2016), AD accounted for 50–70% of these cases (Winblad et al, 2016). 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.Īlzheimer's disease (AD) is the most common neurodegenerative disease. In this review, we evaluate different APP mouse models of AD, and review recent studies using the second‐generation mice. These mice show Aβ accumulation without phenotypes related to overexpression but are not yet a clinical recapitulation of human AD. Second‐generation mouse models contain humanized sequences and clinical mutations in the endogenous mouse App gene. These mice exhibit AD pathology, but the overexpression paradigm may cause additional phenotypes unrelated to AD. ![]() 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). Animal models of human diseases that accurately recapitulate clinical pathology are indispensable for understanding molecular mechanisms and advancing preclinical studies. ![]()
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February 2023
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