The hypothesis is based on the observation ofsignificant loss in cholinergic signaling such as a severe loss of brain white matter with the reduction of cholinergic neurons of the basal forebrain (i.e., Acetylcholine (ACh), nicotine/muscarinic binding sites (nicotinic/muscarinic receptor: nAChR, mAChR)) observed in post-mortem cerebral cortex of AD patients [7]. Here, CHRNA4 is linked to Alzheimer disease.