Introduction and Objective: Chronic Type 2 Diabetes Mellitus (T2DM) is a global health concern, disproportionately affecting African Americans (AA) in the USA. This study investigates gene expression in Amyloid Processing Pathways (APP) and cholesterol biosynthesis-related genes and identifies the key pathways and their roles in linking T2DM to Alzheimer’s Disease (AD) risk in AA.Methods: In this pilot study, six AA participants with T2DM (57.3±4.8y), six normal controls (56.5±4.9y), and three AD (79.3±7.3y) were selected. The whole blood transcriptomic analysis (microarrays) and Ingenuity Pathway Analysis (IPA) were conducted to assess the pathophysiology of T2DM and AD.Results: The signature genes APP, IL18, PSENEN, and MAPK were differentially expressed in the T2DM group. APP was significantly (p-value <0.05) downregulated while MAPT was upregulated. The top canonical pathways(CP) (p-value 0.05) identified were Neuroinflammation Signaling, Insulin receptor signaling, and nNos signaling. The top diseases were Metabolic, Neurological, and Organismal Injury & Abnormalities and their functions (Fx) related to Mild and Moderate Alzheimer’s Disease, and Alzheimer’s Disease Type 3.Conclusion: The study indicates that specific genes and pathways are shared between T2DM and AD, and the insights gained from the study will help identify therapeutic targets and develop therapeutic measures for AD.
J. Sahota: None. S. Ghosh: None. T. Mondal: None. J. Simhadri: None. C. Loffredo: None. C. Howell: None.
National Institutes of Health (5U54MD007597-35)
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