ACHE and early-onset autosomal dominant Alzheimer disease: Recently, the multi-target-directed ligands of histamine receptors gained a lot of attention [45,57,68,78,94,95] that led to development of multi-targeted ligands of H3R, serotonin receptors, as well as acetylcholinesterases (AChE and BuChE), for potential treatment of neurodegenerative diseases such as Alzheimer’s disease.