Comprehensive Evaluation of the 5XFAD Mouse Model for Preclinical Testing Applications: A MODEL-AD Study

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.

Long-term caffeine treatment of Alzheimer mouse models ameliorates behavioural deficits and neuron loss and promotes cellular and molecular markers of neurogenesis

“…We were also unable to detect any alterations in APP processing upon caffeine treatment in the brains of 5xFAD mice, with unchanged levels of full-length APP, total sAPP and sAPP-α. This is in contrast with previous studies [19][20][21] and might be explained by the differences in the experimental models, with earlier, more rapid and robust extracellular Aβ deposition in the 5xFAD model used in the present study [30,31,62].…”

The Therapeutic and Diagnostic Potential of Amyloid β Oligomers Selective Antibodies to Treat Alzheimer’s Disease

“…The Mutant Mouse Resource Research Center (MMRRC) found that Aβ accumulation occurred at different rates, depending on the breeding background, with mice bred on a B6SJL background developing pathology at a significantly more rapid rate (unpublished, available at MMRRC 5xFAD strain data) than those bred on a C57 background. The 5xFAD mouse model is well characterized for memory impairments (Oakley et al, 2006;Kimura and Ohno, 2009;Girard et al, 2013Girard et al, , 2014Zhang M. et al, 2021), neuron loss (Jawhar et al, 2012;Oblak et al, 2021), and Aβ plaque accumulation (Devi et al, 2010;Jawhar et al, 2012;Ashe, 2020;Zhang M. et al, 2021). Comprehensive studies on the 5xFAD model have also looked at cholesterol and glucose levels (Oblak et al, 2021), activity levels (Oblak et al, 2021), neuroinflammation-related protein levels (Ou-Yang and Van Nostrand, 2013;Oblak et al, 2021), tau phosphorylation (Kanno et al, 2014), and visual acuity (Zhang M. et al, 2021).…”

Gamma Oscillations in Alzheimer’s Disease and Their Potential Therapeutic Role

“…Finally, they observed reduction of the tau tangles in a mouse model of tauopathy, indicating the generalization of 40 Hz stimulation effect to other pathogenic proteins. Interestingly, these findings were replicated in several mice models, including WT, 5XFAD, and APP/PSI (i.e., mice genetically engineered to exhibit specific AD pathologies; for reviews see Elder et al, 2010 ; Oblak et al, 2021 ), suggesting that the effects are not specific to one animal model.…”