Following two published articles in 2023, another article on the FAD4T mouse model was published in the first month of 2024! On January 16th, 2024, the paper titled “Alteration of thyroid hormones in mouse models of Alzheimer’s disease and aging” published online in the journal Neuroendocrinology (IF = 5.135) by Yijun Wu ‘s research group from Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. This study used the Alzheimer’s disease (AD) mouse model FAD4T (C57BL/6JGpt-Tg (Thy-APP/Thy-PSEN1) 5/Gpt, T053302) from GemPharmatech as a model for AD and explained the alteration of thyroid hormones (THs) during Alzheimer’s disease and aging, provided new insights into the pathogenesis of these neurodegenerative diseases[1].
The functions of various organs and tissues of the human body gradually decline with aging. AD is one of the most common neurodegenerative diseases which is characterized by cognitive decline and dementia. Epidemiological studies have shown that hypothyroidism and hyperthyroidism are associated with the risk of dementia, among which hypothyroidism is thought to triple the risk of AD[2,3]. However, at present, the relationship between hypothyroidism, aging, and AD remains unclear. Therefore, the researchers performed a thyroid function test and RNA-sequencing (RNA-Seq) analysis using animal models of AD and aging mice. This study found alterations in THs in both FAD4T mice and aging mice. In the thyroid glands of FAD4T mice, the expression of genes related to T cell infiltration and cell proliferation were significantly upregulated, while in the thyroid glands of aging mice, the expression of energy metabolism-related genes were significantly down-regulated. Further analysis showed that these genetic changes were closely related to immune response processes such as immune cell activation and leukocyte migration. This study reveals a new mechanism of THs changes in AD and aging, providing an important reference for in-depth exploration of the pathophysiological processes of these neurodegenerative diseases.
FAD4T mouse model has carry human APP genes with Swedish and Indiana mutations, and human PSEN1 genes carrying M146L and L286V mutations. It can well simulate the disease characterization of clinical AD patients and can also meet relevant pharmacological requirements. At present, 3 related articles have been published, and more articles related to this model are being submitted or reviewed. In addition to this AD mouse model, GemPharmatech also has FAD3T, FAD2T, and AD Plus mouse models which based on FAD4T carrying humanized targets (such as hTREM2, etc.) that have been launched. Feel free to contact us for more detailed data.
References
[1] Zhu S, et al., Alteration of thyroid hormones in mouse models of Alzheimer’s disease and aging. Neuroendocrinology. 2024 Jan 16.
[2] Chaker L, et al., Thyroid function and the risk of dementia: The Rotterdam Study. Neurology. 2016;87(16):1688-95.
[3] Bavarsad K, et al., The effects of thyroid hormones on memory impairment and Alzheimer’s disease. J Cell Physiol. 2019.
