Evaluation of polymorphisms in the presenilin-1 gene and the butyrylcholinesterase gene as risk factors in sporadic Alzheimer's disease

Abstract

The ε4 allele of the apolipoprotein E gene (APOE) is a major risk factor for late-onset Alzheimer's disease (LOAD) but is neither necessary nor sufficient to cause the disease. In this study, we investigated polymorphisms in the presenilin-1 (PS-1), and butyrylcholinesterase (BChE) genes, which have been implicated as risk factors for LOAD. Our data-set comprised 177 AD and 118 control patients, all of whom had been histopathologically confirmed following autopsy. We have tested homozygosity for the PS-1 allele 1 and possession of the BChE-K variant in association with APOE ε4 as risk factors in LOAD. Our findings support an association between the PS-1 polymorphism and LOAD, finding homozygosity for allele 1 associated with an approximately two-fold increased risk. Our data also show that in subjects greater than 75 years of age possession of both BChE-K and APOE-ε4 alleles is associated with an increased risk of LOAD, whilst the risk associated with APOE-ε4 allele alone is not significant.

Genetic Analysis of Alzheimer’s Disease in the Uppsala Longitudinal Study of Adult Men

“…Another gene from this study with association to AD is SELE, which belongs to a group of adhesion molecules expressed by endothelial cells and involved in inflammation processes that could be relevant to AD pathogenesis. We could also detect association of 2 genes that in the past have repeatedly been implicated in AD association studies, BCHE and PSEN1 [26][27][28] . The products of these genes are involved in the metabolic pathways of acetylcholine [32] and amyloid precursor protein (APP) [33,34] , respectively.…”

“…In ULSAM, BMP3 and BMP4 were primarily thought of as candidate genes for osteoporosis, and SELE was initially selected as a gene involved in cardiovascular disease and inflammation. The group of 10 genes with the most significant p values both prior and subsequent to permutation included butyrylcholinesterase (BCHE; MIM 177400) and presenilin 1 (PSEN1; MIM 104311), both previously reported to show association to AD [26][27][28] .…”

Effect of apolipoprotein E and butyrylcholinesterase genotypes on cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease

“…Several groups, including our own, 35 independently replicated this association. [36][37][38] Other investigators found no association. [39][40][41] Some groups have reported a protective effect of BCHE-K genotype on the risk of AD.…”

Lipid homeostasis and apolipoprotein E in the development and progression of Alzheimer's disease

“…Both AChE and APOE have roles in A␤ fibrilization (188,219), and BuChE and APOE have roles in lipid metabolism and transport (13,(220)(221)(222). The BuChE-K polymorphism may also influence the risk of AD conferred by the APOE 4 allele (223,224) and may be associated with slower disease progression in patients with moderate AD (225,226). In patients with mild AD treated with rivastigmine or tacrine for 1 year, the rivastigmine group showed no change in tau concentrations in the CSF, in contrast to significant increases in both tacrine-treated and untreated AD subjects (213).…”