Butyrylcholinesterase: K variant, plasma activity, molecular forms and rivastigmine treatment in Alzheimer's disease in a Southern Brazilian population

Abstract

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.

Serum Cholinesterase Is Inversely Associated with Body Weight Change in Men Undergoing Routine Health Screening

“…Multiple regression analyses confirmed that AD acts as the main factor in plasma BuChE activity reduction and severe stages are related with an even greater reduction (20). These findings suggest that the reduction of plasma BuChE in AD patients is most likely associated with a feedback mechanism and provides a future potential of using this enzyme as a possible secondary marker for AD (20).…”

“…Multiple regression analyses confirmed that AD acts as the main factor in plasma BuChE activity reduction and severe stages are related with an even greater reduction (20). These findings suggest that the reduction of plasma BuChE in AD patients is most likely associated with a feedback mechanism and provides a future potential of using this enzyme as a possible secondary marker for AD (20). A study in middle-aged or elderly men and women (50 years or older) reported that individuals in the lowest quintile of BuChE activity had significantly higher mortality than those in the highest quintile [HRs (95% CI): all-cause mortality, 1.62 (1.15-2.30); cardiovascular deaths, 1.79 (1.05-3.05)] after adjusted for other predictors of mortality by Cox regression methods (21).…”

“…The plasma BuChE activity was significantly lower in patients with Alzheimer's disease (AD) than in elderly controls and a reduction in the plasma BuChE activity was directly associated with AD progression (20). Multiple regression analyses confirmed that AD acts as the main factor in plasma BuChE activity reduction and severe stages are related with an even greater reduction (20).…”

The effect of caffeic acid phenethyl ester (CAPE) on metabolic enzymes including acetylcholinesterase, butyrylcholinesterase, glutathione S-transferase, lactoperoxidase, and carbonic anhydrase isoenzymes I, II, IX, and XII

“…These drugs are used to treat patients with mild-to-moderate AD 128 . BChE has a specific role in cholinergic neurotransmission and it has been associated with AD 129 . Individual ChEIs differ from each other with respect to their pharmacologic properties.…”

“…The human body contains ten times more BChE than AChE 132 . It was reported that in AD, AChE is lost up to 85% in specific brain regions, whereas BChE levels rise with disease progression 129,133 . It was also shown that the main AChE inhibitory effect was primarily associated with aromatic compounds and, to a lesser degree, with aliphatic compounds 134 .…”