Abstract
Alzheimer's disease (AD) is characterized by an extensive loss of cholinergic neurons, and their cortical projections, from the basal forebrain area. The resulting reduction in cholinergic activity is associated with decreased levels of the neurotransmitter acetylcholine (ACh), decreased activity of acetylcholinesterase (AChE), choline acetyltransferase (ChAT), and increased butyrylcholinesterase (BChE) activity. In the present study, we investigated whether the BCHE, ACHE, and CHAT genes were associated with AD and the possibility of a synergistic effect with APOEโฮต4 in a Sardinian sample. AD patients (nโ=โ158), exclusively of Sardinian ancestry, were recruited from the Division of Geriatrics Local Health Agency 8 and Unit of Clinical Pharmacology, Department of Neurosciences, University of Cagliari. Patients were diagnosed according to DSMโIV, and National Institute of Neurologic and Communicative Disorders and StrokeโAD and Related Disorders Association (NINCDSโADRDA) criteria for possible or probable AD. Cognitive screening was performed by means of MiniโMental State Examination (MMSE). Healthy controls (nโ=โ118) of Sardinian ancestry were recruited from religious and sport associations. All patients and control subjects gave informed consent for participation in the study. Single nucleotide polymorphism **(**SNP) analysis was performed by PCR/RFLP or the TaqMan 5โฒ exonuclease method. Our study confirms the association between APOE ฮต4 allele and AD (Pโ<โ0.000). No significant differences were observed in allele and genotype frequencies of BCHE, ACHE, and CHAT between AD and controls. Haplotype analysis of ACHE SNPs did not reveal a significant association between ACHE and AD. Our results suggest that the AChE, ChAT, and BChE polymorphisms do not constitute a major genetic risk factor for susceptibility to AD in a Sardinian population. ยฉ 2007 WileyโLiss, Inc.