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Published on: May 28, 2017
Beyond Transgenic Mice: Emerging Models and Translational Strategies in Alzheimer's Disease
Paula Alexandra Lopes1,2, José L Guil-Guerrero3
1CIISA-Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, Portugal.
Abstract:
Alzheimer's disease (AD) is a leading cause of dementia and a growing public health concern worldwide. Despite decades of research, effective disease-modifying treatments remain elusive, partly due to limitations in current experimental models. The purpose of this review is to critically assess and compare existing murine and alternative models of AD to identify key strengths, limitations, and future directions for model development that can enhance translational relevance and therapeutic discovery. Traditional transgenic mouse models have advanced the understanding of amyloid-beta and tau pathologies, but often fail to capture the complexity of sporadic, late-onset AD. In response, alternative models-including zebrafish, Drosophila melanogaster, Caenorhabditis elegans, non-human primates, and human brain organoids-are gaining traction due to their complementary insights and diverse experimental advantages. This review also discusses innovations in genetic engineering, neuroimaging, computational modelling, and drug repurposing that are reshaping the landscape of AD research. By integrating these diverse approaches, the review advocates for a multi-model, multidisciplinary strategy to improve the predictive power, accelerate clinical translation, and inform personalised therapeutic interventions. Ethical considerations and equitable access to diagnostics and emerging treatments are also emphasised. Ultimately, this work aims to support the development of more accurate, effective, and human-relevant models to combat AD.
Insights
Developing better Alzheimer's disease (AD) models is crucial for finding effective treatments. This review compares traditional mouse models with newer alternatives, advocating for a combined approach to accelerate therapeutic discovery for AD.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Alzheimer's disease (AD) is a major cause of dementia, with limited disease-modifying treatments available.
- Current experimental models, particularly traditional transgenic mice, often fail to fully replicate the complexity of sporadic, late-onset AD.
- This gap in translational relevance hinders the discovery of effective therapies.
Purpose of the Study:
- To critically assess and compare existing murine and alternative models for Alzheimer's disease (AD) research.
- To identify the strengths, limitations, and future directions for developing more translatable AD models.
- To guide enhanced therapeutic discovery and clinical translation for AD.
Main Methods:
- Comprehensive review and comparative analysis of traditional transgenic mouse models and alternative AD models (zebrafish, Drosophila, C. elegans, non-human primates, human brain organoids).
- Discussion of emerging innovations including genetic engineering, neuroimaging, computational modeling, and drug repurposing.
- Consideration of ethical implications and equitable access to diagnostics and treatments.
Main Results:
- Traditional mouse models offer insights into amyloid-beta and tau pathologies but lack the complexity for sporadic, late-onset AD.
- Alternative models provide complementary insights and diverse experimental advantages, showing promise for broader AD research.
- Innovations in technology and a multi-model approach are essential for improving predictive power and accelerating clinical translation.
Conclusions:
- A multi-model, multidisciplinary strategy integrating diverse approaches is advocated to enhance the predictive power of AD research.
- Development of more accurate, effective, and human-relevant models is critical for combating Alzheimer's disease.
- Emphasis on ethical considerations and equitable access is necessary for advancing AD diagnostics and therapeutics.
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