Plasma butyrylcholinesterase activity: a possible biomarker for differential diagnosis between Alzheimer's disease and dementia with Lewy bodies?

Josviak, Nalini Drieli; Batistela, Meire Silva; Souza, Ricardo Krause Martinez de; Wegner, N. R.; Bono, Gleyse Freire; Sulzbach, Carla Daniela; Simão-Silva, Daiane Priscila; Piovezan, Mauro Roberto; Souza, Ricardo Lehtonen Rodrigues de; Furtado-Alle, Lupe

doi:10.1080/00207454.2017.1329203

Cited by 12 publications

(6 citation statements)

References 48 publications

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“…Therefore, high ChAT activity, low activities of AChE and BuChE can predict the occurrence and development of POD before operation, with BuChE as the focus. The decrease in plasma BuChE activity, and its influence have been investigated in diseases with a cholinergic deficit such as AD, and the reduction of total plasma BuChE activity is probably associated with a feedback mechanism providing a perspective for using BuChE as a possible plasmatic marker for AD [29]. At the same time, our study shows that AChE, BuChE and ChAT activities have good correlation between plasma and CSF.…”

Section: Discussionsupporting

confidence: 61%

Cerebrospinal fluid cholinergic biomarkers are associated with postoperative delirium in elderly patients undergoing Total hip/knee replacement: a prospective cohort study

Tang

Liu

et al. 2020

BMC Anesthesiol

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Background Postoperative delirium (POD) is a frequent complication after surgery and its occurrence is associated with poor outcomes. The neuropathology of this complication is unclear, but it is important to evaluate relevant biomarkers for postoperative status. The purpose of this study is to explore the relationship between expression levels of cholinergic biomarkers in cerebrospinal fluid (CSF) and the occurrence and development of POD in elderly patients. Methods Four hundred and ninety-two elderly patients aged 65 years old or older with elective total hip/knee replacement received combined spinal-epidural anesthesia. Preoperative baseline cognitive function was assessed using the Mini-Mental State Examination (MMSE) before surgery. Each patient was interviewed in post-anesthesia care unit (PACU) and on the first, second, third and seventh (or before discharge) postoperative days. POD was diagnosed using the Confusion Assessment Method (CAM), and POD severity was measured using the Memorial Delirium Assessment Scale (MDAS). Preoperative CSF and plasma choline acetyltransferase (ChAT), acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were determined by ELISA. The levels of ChAT, AChE and BuChE activities were determined by spectrophotometry. Results POD was detected in 11.4% (51/447) of the patients. AChE, BuChE, ChAT, TNF-α and IL-6 concentrations in CSF and plasma have higher consistency. In preoperative CSF and preoperative and postoperative plasma, down-regulation of the concentration and activity of AChE and BuChE as well as up-regulation of the concentration and activity of ChAT and the concentrations of IL-6 and TNF-α were observed in patients who developed POD, and the decrease in BuChE was the most obvious. Logistic analysis showed the activities of ChAT, AChE and BuChE in CSF were still related to POD after adjusting for related factors such as sex, age, years of education, height, weight, body mass index (BMI), and American Society of Anesthesiologists (ASA) class. Receiver Operating Characteristic (ROC) curve analysis was conducted to determine the Area Under Curve (AUC) of AChE, BuChE and ChAT activity in CSF was 0.679 (P < 0.01), 0.940 (P < 0.01) and 0.819 (P < 0.01) respectively and found that BuChE activity had the most accurate diagnostic value. Conclusion The changes in preoperative activity of AChE, BuChE and ChAT in CSF were associated with the development of POD in elderly patients, and BuChE activity had the greatest diagnostic value, which may be related to central cholinergic degradation. These cholinergic biomarkers might participate in the neuropathology of POD, pending further investigations. Trial registration This study was registered at Chictr.org.cn (NO. ChiCTR1900023729) June 9th, 2019. (Retrospectively registered).

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Section: Discussionsupporting

confidence: 61%

Cerebrospinal fluid cholinergic biomarkers are associated with postoperative delirium in elderly patients undergoing Total hip/knee replacement: a prospective cohort study

Tang

Liu

et al. 2020

BMC Anesthesiol

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“…The enzyme butyrylcholinesterase (BCHE) is involved in the metabolism of acetylcholine whose deficit is one of the hallmarks of AD and DLB. Recently, a lower BCHE activity was measured in plasma of patients suffering from DLB than in plasma of controls or AD patients 40 , which could be in accordance with the reduced expression of BCHE we have found in plasma-EVs by MS/MS. Nevertheless, using a conventional ELISA we were unable to detect BCHE levels even in the control group.…”

Section: Discussionsupporting

confidence: 84%

Comprehensive proteomic profiling of plasma-derived Extracellular Vesicles from dementia with Lewy Bodies patients

Gámez-Valero

Campdelacreu

Rizzoli

et al. 2019

Sci Rep

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Proteins and nucleic acids contained in extracellular vesicles (EVs) are considered a feasible source of putative biomarkers for physiological and pathological conditions. Within the nervous system, not only neurons but also other brain cells are able to produce EVs, which have been involved in their physiological processes and also in the development and course of several neurodegenerative diseases. Among these, dementia with Lewy bodies (DLB) is the second cause of dementia worldwide, though most cases are missed or misdiagnosed as Alzheimer’s disease (AD) due to the important clinical and pathological overlap between both diseases. In an attempt to find reliable biomarkers for DLB diagnosis, our group characterized the proteome of plasma-derived EVs from DLB patients compared to aged-matched healthy controls (HCs) using two different proteomic LC-MS/MS approaches. Remarkably, we found that gelsolin and butyrylcholinesterase were differentially identified between DLB and HCs. Further validation of these results using conventional ELISA techniques, and including an additional group of AD patients, pointed to decreased levels of gelsolin in plasma-EVs from DLB compared to HCs and to AD samples. Thus, gelsolin may be considered a possible biomarker for the differentiation between DLB and AD.

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“…When the predicted results were further evaluated, BChE-one of the key targets related to the "response to xenobiotic stimulus" pathway-was picked for further validation. As a promising druggable target for AD, BChE activity is significantly elevated in later stages of AD [59][60][61]. Our study indicates that BChE may be a shared target for both AD and hypertension (Table 1).…”

Section: Discussionmentioning

confidence: 64%

A Network-Based Approach to Explore the Mechanisms of Uncaria Alkaloids in Treating Hypertension and Alleviating Alzheimer’s Disease

Zhang

et al. 2020

IJMS

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Uncaria alkaloids are the major bioactive chemicals found in the Uncaria genus, which have a long history of clinical application in treating cardiovascular and mental diseases in traditional Chinese medicine (TCM). However, there are gaps in understanding the multiple targets, pathways, and biological activities of Uncaria alkaloids. By constructing the interactions among drug-targets-diseases, network pharmacology provides a systemic methodology and a novel perspective to present the intricate connections among drugs, potential targets, and related pathways. It is a valuable tool for studying TCM drugs with multiple indications, and how these multi-indication drugs are affected by complex interactions in the biological system. To better understand the mechanisms and targets of Uncaria alkaloids, we built an integrated analytical platform based on network pharmacology, including target prediction, protein–protein interaction (PPI) network, topology analysis, gene enrichment analysis, and molecular docking. Using this platform, we revealed the underlying mechanisms of Uncaria alkaloids’ anti-hypertensive effects and explored the possible application of Uncaria alkaloids in preventing Alzheimer’s disease. These results were further evaluated and refined using biological experiments. Our study provides a novel strategy for understanding the holistic pharmacology of TCM, as well as for exploring the multi-indication properties of TCM beyond its traditional applications.

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Plasma butyrylcholinesterase activity: a possible biomarker for differential diagnosis between Alzheimer's disease and dementia with Lewy bodies?

Cited by 12 publications

References 48 publications

Cerebrospinal fluid cholinergic biomarkers are associated with postoperative delirium in elderly patients undergoing Total hip/knee replacement: a prospective cohort study

Cerebrospinal fluid cholinergic biomarkers are associated with postoperative delirium in elderly patients undergoing Total hip/knee replacement: a prospective cohort study

Comprehensive proteomic profiling of plasma-derived Extracellular Vesicles from dementia with Lewy Bodies patients

A Network-Based Approach to Explore the Mechanisms of Uncaria Alkaloids in Treating Hypertension and Alleviating Alzheimer’s Disease

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