Animal Models of Alzheimer Disease
Open accessAbstract
Significant insights into the function of genes associated with Alzheimer disease and related dementias have occurred through studying genetically modified animals. Although none of the existing models fully reproduces the complete spectrum of this insidious human disease, critical aspects of Alzheimer pathology and disease processes can be experimentally recapitulated. Genetically modified animal models have helped advance our understanding of the underlying mechanisms of disease and have proven to be invaluable in the preclinical evaluation of potential therapeutic interventions. Continuing refinement and evolution to yield the next generation of animal models will facilitate successes in producing greater translational concordance between preclinical studies and human clinical trials and eventually lead to the introduction of novel therapies into clinical practice.
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Current AD animal models have shifted from single genetic mutation models to multi-gene transgenic models, and consider non-genetic pathogenic factors and species differences to more accurately simulate AD progression.
“Current AD animal models have shifted from single genetic mutation models to multi-gene transgenic models, and consider non-genetic pathogenic factors and species differences to more accurately simulate the AD progression process.484–487”
From Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies. (2024) · cites this paper as [486]
The paper describes multigenic transgenic models, including 3xTg-AD mice carrying APP, PS1 and tau mutant transgenes (section on multigenic models; page unavailable). It discusses aging and species differences in the Conclusions (page unavailable), but presents modeling sporadic disease through aging and using other species as future goals, not established features of current models. (LLM, conf=0.88)
Experimental — accuracy not yet measuredGenetically modified mice cannot fully mimic AD and are often viewed as a model of AD asymptomatic stage.
“Genetically modified mice cannot fully mimic AD and are often viewed as a model of AD asymptomatic stage (LaFerla and Green, 2012).”
From Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer’s Disease Progression (2020) · cites this paper as LaFerla and Green, 2012
The Abstract (page unavailable) says no single mouse model recapitulates the full spectrum of AD. The Translational Issues section (page unavailable) adds that many models lack the extensive neuronal loss seen in patients. The paper does not say genetically modified mice are often viewed as models of an asymptomatic stage; it reports cognitive decline in many such mice. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn vivo animal models can recapitulate Alzheimer's disease features by transgenic expression of human familial AD genes, which lead to spontaneous formation of Aβ plaques and neurofibrillary tangles.
“The in vivo animal models can recapitulate AD disease features by the transgenic expression of human familial AD genes which lead to spontaneously formation of Aβ plaques and neurofibrillary tangles.13, 14”
From Acoustofluidic assembly of 3D neurospheroids to model Alzheimer's disease (2020) · cites this paper as [13]
The passages labeled Abstract say that models using familial AD mutations develop Aβ pathology, but APP-overexpressing mice do not develop neurofibrillary tangles. They explain that tangles require additional alterations, such as expression of mutant human tau, so the claim overstates what expression of familial AD genes alone produces. (LLM, conf=0.90)
Experimental — accuracy not yet measuredAnimal models cannot fully recapitulate AD symptoms.
“A large number of animal models have been developed to test these hypotheses, but cannot fully recapitulate AD symptoms (LaFerla and Green, 2012; Sasaguri et al., 2017).”
From Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer’s Disease Progression (2020) · cites this paper as LaFerla and Green, 2012
Animal AD models allow targeted genetic modifications related to AD pathology and evaluation of associated cognitive deficits.
“This allows not only targeted genetic modifications related to AD pathology but also the evaluation of associated cognitive deficits [151].”
From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [151]
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“A large number of animal models have been developed to test these hypotheses, but cannot fully recapitulate AD symptoms (LaFerla and Green, 2012; Sasaguri et al., 2017).”
BackgroundAnimal models of human disease: challenges in enabling translation
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“This allows not only targeted genetic modifications related to AD pathology but also the evaluation of associated cognitive deficits [151].”
BackgroundAnimal models of neurodegenerative diseases
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“A large number of AD mouse models have been extensively characterized, and these systems have contributed to our understanding of disease pathogenesis (Götz et al., 2018; Jankowsky and Zheng, 2017; LaFerla and Green, 2012).”
BackgroundRole of tau protein in Alzheimer’s disease: The prime pathological player
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- Authors
- LaFerla, F. M., & Green, K. N.
- Affiliations
- University of California, Irvine (US)
- ORCID
- LaFerla, F. M.
- Venue
- Cold Spring Harbor Perspectives in Medicine
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2012-09-21
- Volume
- 2
- Issue
- 11
- Pages
- a006320-a006320
- ISSN
- 2157-1422 (ISSN-L)
- PMC
- PMC3543097
- OpenAlex
- W2136623897
- Cited by
- 419
- References
- 89
- Citations by year
- 2026: 8 · 2025: 19 · 2024: 27 · 2023: 30 · 2022: 36 · 2021: 44 · 2020: 42 · 2019: 41 · 2018: 45 · 2017: 29 · 2016: 26 · 2015: 25 · 2014: 30 · 2013: 11 · 2012: 2
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Perspectives in Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Physiology › 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 animals, transgenic mouse model, Alzheimer's disease pathology, preclinical drug testing, translational research, therapeutic interventions
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Humans, Mice, Transgenic, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, Amyloid beta-Protein Precursor, Neurofibrillary Tangles, tau Proteins, Mice, Knockout, Mice, Amyloid Precursor Protein Secretases, Translational Research, Biomedical
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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