Beneficial actions of dietary soy (either whole soy protein, or soy isoflavones) on learning and memory have been reported in both animal and human studies. We report here results of proteomics analyses of brain proteins in rodent brain following dietary soy intake that complements these behavior studies. We hypothesized that the behavioral benefits of soy involved changes at the protein level either in abundance or post-translational modifications that could be detected by 2D gel proteomics, and that identification of such proteins would provide insights for specific signaling or enzyme networks that would enable deeper understanding of whether dietary soy has neuroprotective actions, and whether such actions could be extrapolated to prevention of age-related neurodegeneration. In this study, we administered over 12 months a defined diet AIN-76A where the casein protein had been replaced by either soy protein, or soy protein depleted of the isoflavones, to a transgenic mouse model of Alzheimer’s (AD). The amyloid precursor protein is overexpressed in this mouse model, and the amyloidogenic Ab fragment, Ab<sub>1-42</sub>, accumulates over time as in the brains of AD patients. After 12 mo, 2D gel proteomics analysis revealed that there were proteins that were differentially expressed and/or modified in the brains of mice depending on whether the soy protein had the isoflavones or had been depleted of the latter. Mass spectrometry identified proteins, the majority of which had been shown to be aberrantly expressed in AD brain, and in other mouse models of neurodegeneration. Moreover, the changes in these proteins were for the most part in the opposite direction to those observed in AD brains, and in animal models of neurodegeneration. These results are consistent with the hypothesis that ingestion of soy protein is protective against neurodegeneration, and that the isoflavones may be the bioactive components of soy.

Assessment of the ability of dietary soy to impact age-related neurodegeneration

251st National Meeting (2016)

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