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Might Diet, APOE-APOA1 Axis, and Iron Metabolism Provide Clues About the Discrepancy in Alzheimer’s Disease Occurrence Between Humans and Chimpanzees? A Bioinformatics-Based Re-Analysis of Gene Expression Data on Mice Fed with Human and Chimpanzee Diets

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Abstract

The emergence of conflicting reports on the natural occurrence of Alzheimer’s disease (AD) in non-human primates has prompted research on the comparison of the role of diet-associated changes in gene expression between humans and non-human primates. This article analyzes the effects of different human and chimpanzee diets and their link with apolipoproteins, lipid, and iron (Fe) metabolism, starting from available data, to find out any gap in the existing knowledge. By using a system biology approach, we have re-analyzed the liver and brain RNA seq data of mice fed with either human or chimpanzee diet for 2 weeks to look for genetic differences that may explain the differences in AD occurrence between those two classes. In liver samples of mice fed with the chimpanzee diet in comparison to the human diet, apolipoprotein A-1, ceruloplasmin, and 10 other genes were upregulated while 21 genes were downregulated. However, brain apolipoprotein E4 gene expression was not changed upon diet. Genetic, structural, and functional differences in apolipoprotein E protein, along with differences in Fe metabolisms and a longer lifespan of humans during evolution may account for the observed disparity.

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Acknowledgements

The authors thank Dr. Carl Salustri for critical English editing.

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Authors and Affiliations

  1. Centre for Systems Biology and Bioinformatics, Panjab University, Chandigarh, India

    Ashok Kumar & Parminder Singh

  2. Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Kalyani, West Bengal, 741245, India

    Amit Pal

  3. Department of Biochemistry, Maharishi Markandeshwar College of Medical Sciences and Research (MMCMSR), Sadopur, Ambala, India

    Isha Rani

  4. Digestive and Colorectal Surgery, Ospedale Isola Tiberina, Gemelli Isola, 00186, Rome, Italy

    Vincenzo Tondolo

  5. Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy

    Vincenzo Tondolo

  6. Department of Laboratory Science, Ospedale Isola Tiberina, Gemelli Isola, 00186, Rome, Italy

    Mauro Rongioletti & Rosanna Squitti

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Correspondence to Amit Pal.

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Ashok Kumar, Amit Pal, and Rosanna Squitti are co-first authors.

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ESM 1

File 1. Top differentially expressed genes analyzed by limma in R; File 2. DEGs of Mouse Brain Chimpanzee Diet (experiment) vs Mouse Brain pellet Diet (control); File 3. DEGs of Mouse Brain Human Diet (experiment) vs Mouse Brain pellet Diet (control); File 4. DEGs of Mouse Liver Chimpanzee Diet (experiment) vs Mouse Liver Human Diet (control); File 5. DEGs of Mouse Liver Chimpanzee Diet (experiment) vs Mouse Liver pellet Diet (control); File 6. DEGs of Mouse Liver Human Diet (experiment) vs Mouse Liver pellet Diet (control); File 7. Representative image of protein-protein interaction network between the DEGs in the Mouse Liver Chimpanzee Diet (condition under study) vs. Mouse Liver Human Diet (control); File 8. Representative image for protein-protein interaction network between the DEGs in the Mouse Liver and Brain [Human Diet (condition under study) vs pellet Diet (control)]; File 9. Representative image for protein-protein interaction network between the DEGs in the Mouse Liver and Brain [Chimpanzee Diet (condition under study) vs pellet Diet (control)] (ZIP 2167 kb)

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Kumar, A., Pal, A., Singh, P. et al. Might Diet, APOE-APOA1 Axis, and Iron Metabolism Provide Clues About the Discrepancy in Alzheimer’s Disease Occurrence Between Humans and Chimpanzees? A Bioinformatics-Based Re-Analysis of Gene Expression Data on Mice Fed with Human and Chimpanzee Diets. Biol Trace Elem Res (2023). https://doi.org/10.1007/s12011-023-03932-5

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