Abstract
The ability to investigate therapeutic interventions in animal models of neurodegenerative diseases depends on extensive characterization of the model(s) being used. There are numerous models that have been generated to study Alzheimer’s disease (AD) and the underlying pathogenesis of the disease. While transgenic models have been instrumental in understanding AD mechanisms and risk factors, they are limited in the degree of characteristics displayed in comparison with AD in humans, and the full spectrum of AD effects has yet to be recapitulated in a single mouse model. The Model Organism Development and Evaluation for Late-Onset Alzheimer’s Disease (MODEL-AD) consortium was assembled by the National Institute on Aging (NIA) to develop more robust animal models of AD with increased relevance to human disease, standardize the characterization of AD mouse models, improve preclinical testing in animals, and establish clinically relevant AD biomarkers, among other aims toward enhancing the translational value of AD models in clinical drug design and treatment development. Here we have conducted a detailed characterization of the 5XFAD mouse, including transcriptomics, electroencephalogram, in vivo imaging, biochemical characterization, and behavioral assessments. The data from this study is publicly available through the AD Knowledge Portal.
Highlights
Alzheimer’s disease (AD) is the leading cause of dementia, and there are currently no effective intervention strategies to prevent, slow, or reverse the disease process (Citron, 2010; Karch et al, 2014)
Female 5XFAD and WT mice had higher low-density lipoprotein (LDL) levels (Figure 1B), and lower high-density lipoprotein (HDL) levels (Figure 1C) than males, with no significant difference observed between WT and 5XFAD in females in either lipoprotein
Therapeutic interventions are desperately needed for the treatment of AD, and the development of effective therapeutic strategies is limited by a lack of model organisms with disease characteristics sufficiently similar to that of human AD (Dodart et al, 2002; Duyckaerts et al, 2008; Citron, 2010; LaFerla and Green, 2012; Porquet et al, 2015; Jankowsky and Zheng, 2017)
Summary
Alzheimer’s disease (AD) is the leading cause of dementia, and there are currently no effective intervention strategies to prevent, slow, or reverse the disease process (Citron, 2010; Karch et al, 2014). While transgenic models have been instrumental in understanding AD mechanisms and risk factors, they are limited in the degree of characteristics displayed in comparison with AD in humans, and the full spectrum of AD effects has yet to be recapitulated in a single mouse model (Dodart et al, 2002; Duyckaerts et al, 2008; Porquet et al, 2015; Jankowsky and Zheng, 2017) This incomplete development of AD pathology in EOAD models likely contributes significantly to the difficulty in translating therapeutics developed in EOAD mice to humans in clinical trials to date. No effective treatment has been established for AD (Cavanaugh et al, 2014; Cummings et al, 2014, 2019)
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