Association between butyrylcholinesterase and cerebrospinal fluid biomarkers in Alzheimer's disease patients

作者:Gabriel Antonio Jose*; Almeida Maria Rosario; Ribeiro Maria Helena; Duraes Joao; Tabuas Pereira Miguel; Pinheiro Ana Cristina; Pascoal Rui; Santana Isabel; Baldeiras Ines
来源:Neuroscience Letters, 2017, 641: 101-106.
DOI:10.1016/j.neulet.2017.01.036

摘要

The deficit of cholinergic activity is one of the main findings in Alzheimer's disease (AD), and is related to the synthesis of acetylcholine, and the hydrolysing enzymes, acetylcholinesterase and butyrylcholinesterase (BuChE). Together with the Apolipoprotein E-epsilon 4 allele (ApoE-epsilon 4), the BuChE-K variant has been proposed to increase AD risk in certain populations. In addition, this polymorphism has been associated with a lower capacity to attenuate beta-amyloid aggregation. In the present study we explored the interaction of the BuChE-K variant with its activity in CSF, conventional AD biomarkers and ApoE genotype. 217 AD patients and 200 age-matched controls were genotyped for the ApoE and the BuChE-K variant. BuChE activity in CSF, as well as the levels of the CSF-AD biomarkers amyloid-beta 42 (A beta 42), total and hyperphosphorylated tau (t-tau and p-tau) were determined in 88 of these patients. The results showed no significant differences in the BuChE-K variant distribution between patients and controls. No influence of the BuChE-K variant was seen neither in CSF BuChE activity, nor in the levels of A beta 42, t-tau and p-tau in AD patients. ApoE genotype also did not seem to influence CSF BuChE activity. Interestingly, in AD patients, an association between high CSF BuChE activity and increased levels of CSF A beta 42 was shown, particularly in ApoE-epsilon 4 allele carriers. In our population, the BuChE-K variant does not seem to confer risk for AD or to influence the activity of the enzyme in CSF. However, we demonstrated an association between BuChE activity, ApoE-epsilon 4 genotype and CSF A beta 42 levels, highlighting the importance of assessing BuChE activity as a possible modulator of A beta load in the brain.

  • 出版日期2017-2-22