To our knowledge, we are the first to investigate Riva/HMTM combination treatment in tau models of AD at multiple levels/systems of the brain, and have demonstrated decreased pharmacological efficacy of combination therapy in the regulation of hippocampal acetylcholine [15], synaptosomal glutamate release and mitochondrial activity [34,81], and the presynaptic expression of SNARE proteins involved in synaptic vesicle docking and fusion [82]. Here, MAPT is linked to Alzheimer disease.