AD Animal Models

The development of an animal model of Alzheimer's disease (AD) that best approximates the human disease has been the goal of many researchers. Creative Biolabs specializes in neuroscience research and has extensive project experience. We are also flexible enough to meet the unique needs of our neurological research clients.

Neuropathology of AD

AD is the most common cause of the progressive decline of cognitive function in aged humans and is characterized by the presence of numerous senile plaques and neurofibrillary tangles accompanied by neuronal loss. Information on mechanisms of AD pathogenesis and preclinical evaluation of treatments directed at Aβ or phospho-tau has come from pathology, genetics, and various transgenic rodent models of AD.

Fig.1 Stages in the neuropathology of AD. (Schraen, 2008)

Animal models for AD

To better understand the role of β-amyloid plaques and neurofibrillary tangles (NFTs) in AD and related disorders, experimental animal models have been developed, which reproduce aspects of the neuropathological characteristics of these diseases. These animal models not only provide a general proof of principle but also reproduce more specific aspects of human disease. Animal models have been widely used to identify disease modifiers, pathogenic agents, susceptibility genes, as well as drug screenings. Finally, insight gained from these models can be translated to human disease and assist in the development of potential therapies.

• Natural Models

Some animals, including polar bears, sheep, dogs, goats, cats, and some non-human primates, spontaneously exhibit some of the neuropathological features associated with AD. In recent years, dogs have been considered a useful animal model for AD due to the proximity of canine and human brain aging. Among the non-human primate models, mouse lemurs seem to be a potential animal model that exhibits amyloid plaque, NFTs, and some other AD-related neuropathology.

• Genetic Models

Transgenic technology offers a unique opportunity to reproduce the etiology of familial AD by transfecting mutated human amyloid precursor protein (APP).

1) APP Transgenic mouse models

APP mono-transgenic mouse models showed that Aβ plays a role in progressive plaque formation, synaptic loss, and glial proliferation. Biogenic models confirmed a disease-enhancing role for the β-secretase BACE and the γ-secretase component PS1, various inflammatory molecules, and the ε4 allele of apolipoprotein E.

2) Tau transgenic mouse models

Overexpression of human tau can lead to central and peripheral axonopathy, resulting in nerve cell dysfunction and amyotrophy. Behavioral analysis of tau transgenic mice showed that tau aggregation was sufficient to cause behavioral defects in the absence of NFT formation.

Fig.2 Reproducing plaques and NFTs in transgenic mice. (Woodruff-Pak, 2008)

• Interventional Models

The introduction of pharmacological or chemical agents into the brain, or induction of lesions in specific brain regions, can replicate some of the characteristics of AD. As a disease model, interventional models are generally better at identifying symptomatic or corrective treatments than disease-modifying therapies that stop or slow disease progression.

The study of these animal models is of great significance for clarifying the characteristics and Spatio-temporal evolution of brain cell abnormalities in AD patients, describing the mechanisms leading to brain dysfunction, and identifying new therapeutic targets and approaches. At Creative Biolabs, we have the expertise to optimize each stage to ensure you get the desired outcome, achieving the highest levels of efficiency throughout. Our team of highly qualified and experienced technical staff will work with you to develop and deliver AD animal model solutions. Please feel free to contact us for more detail.

References

1. Schraen, M.S.; et al. Tau as a biomarker of neurodegenerative diseases. 2008.
2. Woodruff-Pak, D.S. Animal models of Alzheimer's disease: therapeutic implications. Journal of Alzheimer's disease. 2008, 15(4): 507-521.