Mutation screening of the CHRNA4 and CHRNB2 nicotinic cholinergic receptorgenes in Alzheimer's disease

POTENTIAL genomic changes leading to decreased nicotine-binding, crucial fo r cognitive dysfunction in Alzheimer's disease (AD), have not yet been stud ied, A search for mutations:of the genes coding for the most widely-distrib uted nicotinic receptor subtype alpha 4 beta 2 (CHRNA4/CHRNB2) has been per formed in AD patients by screening the coding regions of both genes by sing le strand conformation analysis and heteroduplex analysis of fibroblast-der ived genomic DNA. Polymorphisms in CHRNA4, none of which led to amino acid changes in the predicted sequence, were found in three patients. Although t he other receptor subunits have yet to be screened, it appears likely that the reduction of nicotine binding sites in AD is not due to genomic changes . (C) 1999 Lippincott Williams & Wilkins.