In clusters 4, 5, 8 and 21 which have progressive decreases in AD/control ratios as pathological severity increases (Fig. 5), we observe pathways involved in synaptic function are decreased including glutamate signalling, synaptic long term potentiation, GABA receptor signalling, CREB signalling, and synaptic long-term depression. The gene discussed is CREB1; the disease is Alzheimer disease.