Abstract: A novel form of acetylcholinesterase (AChE) is provided, N-AChE, which bears a transmembrane domain. Exons encoding this novel form, the peptide comprising, the transmembrane domain, as well as antibodies recognizing the same are also provided. N-AChE expression in the hippocampus is correlated with Alzheimer's disease. Secreted forms of AChE are also provided, and methods of producing AChE protein are, also described.

Abstract: The invention relates to a method and system for evaluating an effect on the nervous system of a test drug by comparing the effect of such drug on AChE catalytic activity or isoform variance in the brain of a test animal following challenge by an AChE blocker (e.g. DFP) or a blocker of AChE and muscarinic receptors M1 and M2 (e.g. pyridostigmine) and comparing this effect with that of a known agent, preferably a non-selective muscarinic receptor blocker (e.g. scopolamine) or a specific M1 receptor blocker (e.g. pirenzepine). Also provided is a method of screening for a candidate drug that is a modulator of the expression of any one of AChE variants and isoforms by determining the effect of such drug on the translocation of an AChE isoform within a neuron. Further provided is a method of screening for a candidate drug aimed at affecting central nervous system properties which is a modulator of the interaction between AChE-R/RACK1/PKC.