Rodent Models of Amyloid-Beta Feature of Alzheimer's Disease: Development and Potential Treatment Implications

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide and causes severe financial and social burdens. Despite much research on the pathogenesis of AD, the neuropathological mechanisms remain obscure and current treatments have proven ineffective. In the past decades, transgenic rodent models have been used to try to unravel this disease, which is crucial for early diagnosis and the assessment of disease-modifying compounds. In this review, we focus on transgenic rodent models used to study amyloid-beta pathology in AD. We also discuss their possible use as promising tools for AD research. There is still no effective treatment for AD and the development of potent therapeutics are urgently needed. Many molecular pathways are susceptible to AD, ranging from neuroinflammation, immune response, and neuroplasticity to neurotrophic factors. Studying these pathways may shed light on AD pathophysiology as well as provide potential targets for the development of more effective treatments. This review discusses the advantages and limitations of these models and their potential therapeutic implications for AD.

Keywords: Alzheimer’s disease; amyloid-beta; neuroinflammation; neuroplasticity; neurotrophic factors.

Figure 1.

Timeline illustrating the development of transgenic mouse and rat models of AD.

Figure 2.

Human APP695 and APP751 are essential genes involved in the generation of transgenic rodent models of Alzheimer’s disease (AD). Swedish (red), Iberian / Florida (Black) and Indiana / London (Green) are the major mutations introduced into the human APP in rodents to induce rapid amyloid plaque formation. One of the rodent models that encompass numerous mutations is 5XFAD, 3 mutations of which are located on human APP751. Representative photomicrographs showing intense amyloid plaque formation in various brain regions demonstrate severe Aβ pathology in 5XFAD mouse model in the age of 6 months. These images highlight the Aβ pathological progression in brain regions established for memory processes.