BuChE K variant is decreased in Alzheimer's disease not in fronto-temporal dementia.
ABSTRACT Alzheimer's disease (AD) is characterized by a significant reduction in AcetylCholinesterase and an increase in ButyrylCholinesterase (BuChE) activity. The existence of polymorphic regions on the BuChE gene has been previously described; the most frequently found polymorphism is the so-called K variant, which leads to a 30% decreased enzymatic activity. Different studies reported a positive association between K variant and AD, strongest among late-onset AD and Apolipoprotein E (APOE) e4 carriers. We analyzed APOE and BuChE polymorphisms in 167 AD and 59 fronto-temporal dementia (FTD) patients compared with 129 healthy controls (HC). We reported a significantly lower frequency of the BuChE K variant in AD compared with HC and FTD and a significant increased frequency of the K variant in FTD. These results are in agreement with the known increase of the BuChE activity in AD and support the evidence of different molecular pathways involved in the pathogenesis of AD and FTD.
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ABSTRACT: Objective: To examine the role of butyrylcholinesterase (BuChE) in cholinergic signaling and neurologic conditions, such as Alzheimer's disease (AD). The rationale for inhibiting cholinesterases in the management of AD, including clinical evidence supporting use of the dual acetylcholinesterase (AChE) and BuChE inhibitor rivastigmine, is discussed. Data Sources: PubMed searches were performed using butyrylcholinesterase as a keyword. English-language articles referenced in PubMed as of September 2011 were included. Study Selection and Data Synthesis: English-language articles related to BuChE considered to be of clinical relevance to physicians were included. English-language articles specifically related to AChE were not included, as the role of AChE in cholinergic signaling and the underlying pathology of AD is well documented. Reference lists of included publications were used to supplement the search. Results: AChE and BuChE play a role in cholinergic signaling; BuChE can hydrolyze acetylcholine and compensate for AChE when levels are depleted. In the AD brain, AChE levels decrease, while BuChE levels are reportedly increased or unchanged, with changes becoming more pronounced during the disease course. Furthermore, BuChE genotype may influence AD risk and rate of disease progression. Strategies that increase acetylcholine levels (eg, cholinesterase inhibitors) demonstrate symptomatic efficacy in AD. Rivastigmine has proven cognitive efficacy in clinical trials, and data suggest that its action is mediated, in part, by inhibition of BuChE. Retrospective analyses of clinical trials provide evidence that BuChE genotype may also influence treatment response. Conclusions: AChE-selective inhibitors and a dual AChE and BuChE inhibitor demonstrate symptomatic efficacy in AD. Mounting preclinical and clinical evidence for a role of BuChE in maintaining normal cholinergic function and the pathology of AD provides a rationale for further studies investigating use of rivastigmine in AD and the influence of BuChE genotype on observed efficacy.The primary care companion to CNS disorders. 01/2013; 15(2).
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ABSTRACT: In Alzheimer's disease (AD) a reduction in acetylcholinesterase (AChE) and an increase in butyrylcholinesterase (BChE) activity are observed. K variant (539T) is the most common variant of the BCHE gene and, although controversial, several studies reported association between K variant and AD. Previous results showed that the K variant alone is not capable of diminishing BChE activity, depending on the presence of the -116A variant. Considering that, we conducted a case-control association study using a clinically well defined group of AD patients (n=82) and age and sex matched control subjects (EC; n=78) in order to test the association with these variations of BCHE gene in a Brazilian population. The allele, genotype and haplotype frequencies of the K and the -116A variants of BCHE gene were not significantly different between cases and controls. Although not reaching statistical significance, the results suggested that the presence of -116A variant may have a protective effect against AD. The association of the K variant with AD in a controversial manner in different surveys is probably caused by its linkage disequilibrium with -116A that, by reducing BChE activity, potentially increases cholinergic transmission in comparison with usual genotypes.Chemico-biological interactions 03/2013; 203:358-360. · 2.46 Impact Factor
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ABSTRACT: The extensive neuroprotective effects of estrogen against Alzheimer's disease (AD) have been proven in numerous laboratory studies. However, in clinical studies, the exact role of estrogen in AD is still ambiguous. Some evidences even suggested the high levels of estrogen or estrogen replacement treatment increased the risk of AD. Thus, there must be other factors affecting the neuroprotective effects of estrogen. Multiple enzymes and receptor proteins are involved in the biosynthesis, metabolism and signaling pathways of estrogen, and mediate the beneficial effects of estrogen on AD. Previous studies have suggested some polymorphisms of genes encoding these enzymes and proteins are associated with the risk of AD. In addition to the genes associated with estrogen biosynthesis and metabolism and the genes encoding estrogen receptor proteins, some other genes also modulate the effects of estrogen on AD, or interact with other estrogen-associated genes on the progress of AD. The gene-hormone and gene-gene interactions may be key to unraveling the conflicting results regarding the effect of estrogen on AD. In this paper, we will review and discuss the associations between polymorphisms of these genes and their interactions and the susceptibility to AD. A better understanding of these estrogen-associated genes is significant to explore the pathogenesis of AD.Progress in Neurobiology 10/2013; · 9.04 Impact Factor