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Rodent models for Alzheimer’s disease drug discovery
Open accessAbstract
INTRODUCTION: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory loss and personality changes, leading to dementia. Histopathological hallmarks are represented by aggregates of beta-amyloid peptide (Aβ) in senile plaques and deposition of hyperphosphorylated tau protein in neurofibrillary tangles in the brain. Rare forms of early onset familial Alzheimer's disease are due to gene mutations. This has prompted researchers to develop genetically modified animals that could recapitulate the main features of the disease. The use of these models is complemented by non-genetically modified animals. AREAS COVERED: This review summarizes the characteristics of the most used transgenic (Tg) and non-Tg models of AD. The authors have focused on models mainly used in their laboratories including amyloid precursor protein (APP) Tg2576, APP/presenilin 1, 3xAD, single h-Tau, non-Tg mice treated with acute injections of Aβ or tau, and models of physiological aging. EXPERT OPINION: Animal models of disease might be very useful for studying the pathophysiology of the disease and for testing new therapeutics in preclinical studies but they do not reproduce the entire clinical features of human AD. When selecting a model, researchers should consider the various factors that might influence the phenotype. They should also consider the timing of testing/treating animals since the age at which each model develops certain aspects of the AD pathology varies.
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“Meanwhile, being entirely derived from human cells, these organoids can fully replicate human biology and potentially reduce the translational barriers from experimental findings to therapeutic applications (20–22), offering advantages over animal models (23–25).”
From Understanding monocyte-driven neuroinflammation in Alzheimer’s disease using human cortical organoid microphysiological systems (2025) · cites this paper as [23]
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Sasaguri, H., Nilsson, P., Hashimoto, S., Nagata, K., Saito, T., De Strooper, B., Hardy, J., Vassar, R., Winblad, B., & Saido, T. C. (2017) · The EMBO Journal · doi:10.15252/embj.201797397 · Cited by 793
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Gulisano, W., Maugeri, D., Baltrons, M. A., Fà, M., Amato, A., Palmeri, A., D’Adamio, L., Grassi, C., Devanand, D. P., Honig, L. S., et al. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179935 · Cited by 313
Self-citation
Metadata
- Authors
- Puzzo, D., Gulisano, W., Palmeri, A., & Arancio, O.
- Affiliations
- University of Catania (IT)
- Columbia University (US)
- Venue
- Expert Opinion on Drug Discovery
- Publisher
- Informa UK Limited
- Published
- 2015-04-30
- Volume
- 10
- Issue
- 7
- Pages
- 703-711
- ISSN
- 1746-0441 (ISSN-L)
- 1746-045X
- PMC
- PMC4592281
- OpenAlex
- W1963514255
- Cited by
- 222
- References
- 91
- Citations by year
- 2026: 11 · 2025: 18 · 2024: 13 · 2023: 24 · 2022: 19 · 2021: 25 · 2020: 16 · 2019: 19 · 2018: 30 · 2017: 22 · 2016: 22 · 2015: 3
- FWCI
- 3.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Expert Opinion on Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG034248, AG034248)
- National Institute of Neurological Disorders and Stroke (R01NS049442, NS49442)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, animal models, transgenic mice, APP/PS1 double transgenic mice, amyloid-beta, tau protein, amyloid plaques, neurofibrillary tangles, presenilin 1, amyloid precursor protein, physiological aging, drug discovery, preclinical testing
- MeSH terms
- Aging, Alzheimer Disease, Animals, Disease Models, Animal, Drug Evaluation, Preclinical, Humans, Mice, Transgenic, Rodentia, Species Specificity, Mice, Drug Discovery
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