IBB PAS Repository

Synergy between the alteration in the N-terminal region of butyrylcholinesterase K variant and apolipoprotein E4 in late-onset Alzheimer’s disease

Jasiecki, Jacek and Limon-Sztencel, Anna and Chmara, Magdalena and Żuk, Monika and Cysewski, Dominik and Limon, Janusz and Wasąg, Bartosz (2019) Synergy between the alteration in the N-terminal region of butyrylcholinesterase K variant and apolipoprotein E4 in late-onset Alzheimer’s disease. Scientific Reports, 9 (5223). ISSN 2045-2322

[img] PDF
1MB

Official URL: https://www.nature.com/articles/s41598-019-41578-3

Abstract

While the life expectancy of the population has increased, Alzheimer’s disease (AD) has emerged as one of the greatest health problems of old age. AD is characterized by neuronal loss and cognitive decline. In the AD brain, there is a decrease in levels of acetylcholinesterase (AChE) and an increase in the levels of the related enzyme butyrylcholinesterase (BChE), that accumulate in plaques and tangles. Apolipoprotein E (ApoE) is a major cholesterol carrier and plays an important role in maintaining lipid homeostasis. APOE-ε4 constitutes the most important known genetic risk factor for late-onset AD. It has been proposed that the BCHE-K allele (Ala539Thr) acts in synergy with the APOE-ε4 allele to promote risk for AD. However, there is insufcient evidence to support a correlation. Most studies focused only on the coding regions of the genes. In this study, we analyzed sequence regions beyond the BCHE coding sequence. We found synergy between APOE-ε4 and SNPs localized in 5′UTR (rs1126680) and in intron 2 (rs55781031) of the BCHE-K allele (rs1803274) in 18% of patients with late-onset AD (n=55). The results show that the coexistence of the APOE-ε4 allele and 3 SNPs in the BCHE gene is associated with a highly elevated risk of late-onset AD. SNP (rs1126680) in 5′UTR of the BCHE gene is located 32 nucleotides upstream of the 28 amino acid signal peptide. Mass spectrometry analysis of the BChE protein produced by SNP (rs1126680) showed that the mutation caused an in frame N-terminal extension of 41 amino acids of the BChE signal peptide. The resultant variant with a 69 amino acid signal peptide, designated N-BChE, may play a role in development of AD.

Item Type:Article
Subjects:Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
Divisions:Mass Spectrometry Laboratory
ID Code:1713
Deposited By: Dominik Cysewski
Deposited On:24 Apr 2019 08:02
Last Modified:24 Apr 2019 09:01

Repository Staff Only: item control page