Nonclassical roles of cholinesterases in the embryonic brain and possible links to Alzheimer disease.

Evidence about nonclassic functions of acetyl- (AChE) and butyryl-cholinesterase (BChE) during embryonic development of vertebrate brains is compared with evidence of their expression in Alzheimer disease (AD). Before axons extend in the early neural tube, BChE expression shortly precedes the expression of AChE. BChE is associated with neuronal and glial cell proliferation, and it may also regulate AChE. AChE is suggested to guide and stabilize growing axons. Pathologically, cholinesterase expression in AD shows some resemblance to that in the embryo. These findings are inconsistent with the "cholinergic hypothesis." Rather, it is suggested that cholinesterases in AD function nonclassically as in the embryo, possibly as part of a "neoembryonic" restorative program. These views may open new strategies for pharmacology and therapy for AD.