Weighted gene co-expression network analysis (WGCNA) was performed using the GeneMANIA plugin [39] for Cytoscape version 3.7.2 (Cytoscape Consortium, San Diego, CA, USA) [49]. Networks were created using the IMPaLA-generated lists of DEGs enriched in KEGG pathways associated with (1) Diabetes and dementia (n = 73, P < 0.05) (Additional file 1: Fig. S1), (2) Diabetic complications (n = 101, P < 0.05) (Additional file 2: Fig. S2), (3) DNA damage response (n = 87, P < 0.05) (Additional file 3: Fig. S3a), and (4) Autophagy (n = 31, P < 0.001) (Additional file 3: Fig. S3b). The Diabetes and dementia network included insulin signalling, AGE-RAGE signalling in diabetic complications, and Alzheimer disease. The Diabetic complications network included AGE-RAGE signalling in diabetic complications, chemokine signalling (inflammation), hypoxia inducible factor-1 (HIF-1) signalling, fluid shear stress and atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). The DNA damage response network included cell cycle, cellular senescence, p53 signalling, apoptosis, and necroptosis (inflammatory cell death). The brain NVU was analysed as a whole. Network weighting was assigned based on query genes, so as to maximise connectivity among input genes. The maximum number of related genes or attributes was zero [18, 65]. Two gene products are linked in red, if they participated in the same reaction within a pathway [67]. The strengths of relationships are represented by the intensity of the colour and the thickness of the interconnecting lines.

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