Glycosylation of acetylcholinesterase and butyrylcholinesterase changes as a function of the duration of Alzheimer's disease

Abstract

The identification of biochemical markers of Alzheimer's disease (AD) may help in the diagnosis of the disease. Previous studies have shown that Abeta(1-42) is decreased, and tau and phospho-tau are increased in AD cerebrospinal fluid (CSF). Our own studies have identified glycosylated isoforms of acetylcholinesterase (Glyc-AChE) and butyrylcholinesterase (Glyc-BuChE) that are increased in AD CSF. Glyc-AChE is increased in APP (SW) Tg2576 transgenic mice prior to amyloid plaque deposition, which suggests that Glyc-AChE may be an early marker of AD. The aim of this study was to determine whether Glyc-AChE or Glyc-BuChE is increased in CSF at early stages of AD and to compare the levels of these markers with those of Abeta(1-42), tau and phospho-tau. Lumbar CSF was obtained ante mortem from 106 non-AD patients, including 15 patients with mild cognitive impairment (MCI), and 102 patients with probable AD. Glyc-AChE, tau and phospho-tau were significantly increased in the CSF of AD patients compared to non-neurological disease (NND) controls. Abeta(1-42) was lower in the AD patients than in NND controls. A positive correlation was found between the levels of Glyc-AChE or Glyc-BuChE and disease duration. However, there was no clear correlation between the levels of tau, phospho-tau or Abeta(1-42) and disease duration. The results suggest that Glyc-AChE and Glyc-BuChE are unlikely to be early markers of AD, although they may have value as markers of disease progression.

The role of protein glycosylation in Alzheimer disease

“…Likewise, the related compound butyrylcholinesterase is differently glycosylated in AD, and both of these cholinesterases have been suggested to be biomarkers for AD [83,84]. The changes in glycosylation of these proteins, however, occur relatively late in the course of disease progression, and are therefore not likely to be early biomarkers [85]. In fact, it has been suggested that both Ab and tau induce the altered glycosylation of the cholinesterases [78].…”

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

“…[85][86][87][88][89][90] Other than in aged nondemented individuals, normal CSF T-tau is found in depression, alcoholic dementia, and in chronic neurological disorders such as Parkinson's disease (PD) and progressive supranuclear palsy. 14,20,50,52,57,63,70,85,88,89,91 Thus, CSF T-tau has a clear clinical diagnostic value in the differentiation between AD and these important and often difficult differential diagnoses.…”

Large-scale studies of the functional K variant of the butyrylcholinesterase gene in relation to Type 2 diabetes and insulin secretion

“…The BCHE gene (3q26) is expressed in many tissues including white adipose tissue, liver, brain and pancreas [5,6] and may have a direct biological impact on the pathogenesis of the amyloidosis related to Alzheimer's disease [7]. Several variants have been identified in BCHE, the most common being a point mutation at nucleotide 1615 (GCA to ACA) predicting an alanine to threonine substitution at codon 539 [8,9].…”