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Publications

Journal Article Review Epublish

PubMed: 40565005 DOI: 10.3390/ijms26125541

Beyond Transgenic Mice: Emerging Models and Translational Strategies in Alzheimer's Disease.

Int J Mol Sci 26(12)

Authors: Paula Alexandra Lopes, José L Guil-Guerrero

Affiliations

  • CIISA-Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, Portugal.
  • Laboratório Associado para Ciência Animal e Veterinária (AL4AnimalS), Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, Portugal.
  • Departamento de Tecnología de Alimentos, Universidad de Almería, 04120 Almería, Spain.

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.

MeSH

Alzheimer Disease, Translational Research, Biomedical, Multiple Chronic Conditions, Research, Therapeutics