CHRNA4 and Alzheimer disease: Furthermore, the nAChR is implicated in the pathology of AD, as cholinergic depletion may elevate Aβ production and its neurotoxicity by altering the signal conduction event (reduced acetylcholine synthesis caused by reduced choline acetyltransferase activity, which in turn reduces cholinergic receptor activation, ultimately leading to a reduction in cAMP and a decrease in protein kinase activity) associated with cholinergic neurotransmission [53].