Bono G F, Simão-Silva D P, Batistela M S, Josviak N D, Dias P F R, Nascimento G A, Souza R L R, Piovezan M R, Souza R K M, Furtado-Alle L
Department of Genetics, Federal University of Paraná, Curitiba, Brazil.
Department of Genetics, Federal University of Paraná, Curitiba, Brazil.
Neurochem Int. 2015 Feb;81:57-62. doi: 10.1016/j.neuint.2014.12.009. Epub 2015 Jan 23.
Alzheimer's disease (AD) is a neurodegenerative disorder in which there is a decline of cholinergic function. The symptomatic AD treatment involves the use of ChEIs (cholinesterase inhibitors) as rivastigimine, a dual inhibitor. The human butyrylcholinesterase (BChE) is an enzyme that has specific roles in cholinergic neurotransmission and it has been associated with AD. In the serum, BChE is found in four main molecular forms: G1 (monomer); G1-ALB (monomer linked to albumin); G2 (dimer); and G4 (tetramer). The interaction between the products of BCHE gene and CHE2 locus results in CHE2 C5+ and CHE2 C5- phenotypes. CHE2 C5+ phenotype and BChE-K are factors that influence on BChE activity. This work aimed to verify the proportions of BChE molecular forms, total and relative activity in 139 AD patients and 139 elderly controls, taking into account K variant, CHE2 locus, rivastigmine treatment and clinical dementia rating (CDR) of AD patients. Phenotypic frequencies of CHE2 C5+ and frequency of the carriers of the K allele were similar between groups. Total BChE activity in plasma was significantly lower in AD patients than in elderly controls. Furthermore, we found that reduction on plasma BChE activity is associated directly with AD progression in AD patients and that rivastigmine treatment has a stronger effect on BChE activity within the CDR2 group. The reduction in BChE activity did not occur proportionally in all molecular forms. Multiple regression analysis results confirmed that AD acts as the main factor in plasma BChE activity reduction and that severe stages are related with an even greater reduction. These findings suggest that the reduction of total plasma BChE and relative BChE molecular forms activity in AD patients is probably associated with a feedback mechanism and provides a future perspective of using this enzyme as a possible plasmatic secondary marker for AD.
阿尔茨海默病（AD）是一种神经退行性疾病，其胆碱能功能会下降。AD的症状性治疗包括使用胆碱酯酶抑制剂（ChEIs），如利伐斯的明这种双重抑制剂。人丁酰胆碱酯酶（BChE）是一种在胆碱能神经传递中具有特定作用的酶，并且与AD有关。在血清中，BChE以四种主要分子形式存在：G1（单体）；G1-ALB（与白蛋白相连的单体）；G2（二聚体）；以及G4（四聚体）。BCHE基因产物与CHE2基因座之间的相互作用导致CHE2 C5+和CHE2 C5-表型。CHE2 C5+表型和BChE-K是影响BChE活性的因素。这项研究旨在验证139例AD患者和139例老年对照中BChE分子形式的比例、总活性和相对活性，同时考虑K变体、CHE2基因座、利伐斯的明治疗以及AD患者的临床痴呆评定量表（CDR）。两组之间CHE2 C5+的表型频率和K等位基因携带者的频率相似。AD患者血浆中的总BChE活性显著低于老年对照。此外，我们发现血浆BChE活性的降低与AD患者的AD进展直接相关，并且利伐斯的明治疗对CDR2组内的BChE活性有更强的影响。并非所有分子形式的BChE活性都成比例降低。多元回归分析结果证实，AD是血浆BChE活性降低中的主要因素，并且严重阶段与更大程度的降低相关。这些发现表明，AD患者血浆总BChE和相对BChE分子形式活性的降低可能与一种反馈机制有关，并为将这种酶用作AD可能的血浆二级标志物提供了未来的研究方向。
