APOE and Alzheimer disease: Clusters 1 and 2, which included proteins highly upregulated in AD APOE4 BA41/42 compared to the other groups indicate increases in pathways involved in actin cytoskeleton signalling, NRF2 mediated oxidative stress response, PDGF signalling, and insulin receptor signalling, which all implicate non-neuronal contributors to synapse degeneration as has been recently emphasised for AD risk by genetic studies [18].