Background: In Alzheimer's disease (AD), brain butyrylcholinesterase (BChE) co-localizes with beta-amyloid (Abeta) fibrils.
Aims: In vitro testing of the significance of this phenomenon to AD progress.
Methods: A thioflavine T (ThT) fluorogenic assay, photo-induced cross-linking and quantifiable electron microscopy served to compare the effect on Abeta fibril formation induced by highly purified recombinant human BChE (rBChE) produced in the milk of transgenic goats with that of serum-derived human BChE.
Results: Both proteins at 1:50 and 1:25 ratios to Abeta dose-dependently prolonged the ThT lag time and reduced the apparent rate of Abeta fibril formation compared to Abeta alone. Photo-induced cross-linking tests showed that rBChE prolonged the persistence of amyloid dimers, trimers and tetramers in solution, whereas Abeta alone facilitated precipitation of such multimers from solution. Transmission electron microscopy showed that rBChE at 1:100 to Abeta prevented the formation of larger, over 150-nm-long, Abeta fibrils and reduced fibril branching compared to Abeta alone as quantified by macro programming of Image Pro Plus software.
Conclusion: Our findings demonstrate that rBChE interacts with Abeta fibrils and can attenuate their formation, extension and branching, suggesting further tests of rBChE, with unlimited supply and no associated health risks, as a therapeutic agent for delaying the formation of amyloid toxic oligomers in AD patients.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1159/000113711 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Machine learning models for dementia screening to classify brain amyloid positivity on positron emission tomography using blood markers and demographic characteristics: a retrospective observational study.
Alzheimers Res Ther
January 2025
Department of Neurology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan.
Background: Intracerebral amyloid β (Aβ) accumulation is considered the initial observable event in the pathological process of Alzheimer's disease (AD). Efficient screening for amyloid pathology is critical for identifying patients for early treatment. This study developed machine learning models to classify positron emission tomography (PET) Aβ-positivity in participants with preclinical and prodromal AD using data accessible to primary care physicians.
View Article and Find Full Text PDFExploring the ability of plasma pTau217, pTau181 and beta-amyloid in mirroring cerebrospinal fluid biomarker profile of Mild Cognitive Impairment by the fully automated Lumipulse platform.
Fluids Barriers CNS
January 2025
Neurology 5 - Neuropathology Unit, Fondazione IRCCS - Istituto Neurologico Carlo Besta, Via Celoria 11, Milan, 20133, Italy.
Background: The approval of new disease-modifying therapies by the U.S. Food and Drug Administration and the European Medicine Agency makes it necessary to optimize non-invasive and cost-effective tools for the identification of subjects at-risk of developing Alzheimer's Disease (AD).
View Article and Find Full Text PDFUncovering cerebral blood flow patterns corresponding to Amyloid-beta accumulations in patients across the Alzheimer's disease continuum using the arterial spin labeling.
Neurol Sci
January 2025
School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder ranging from mild cognitive impairment (MCI) to AD dementia. Abnormal cerebral perfusion alterations, influenced by amyloid-beta (Aβ) accumulations, have been implicated in cognitive decline along this spectrum.
Objective: This study investigates the relationship between cerebrospinal fluid (CSF) Aβ1-42 levels and regional cerebral blood flow (CBF) changes across the AD continuum using the Arterial Spin Labeling (ASL) technique.
Charge Modification of Lysine Mitigates Amyloid-β Aggregation.
Chembiochem
January 2025
Yonsei University, Deparment of Pharmacy, 85 Songdogwahak-ro, Yeonsu-gu, Yonsei University, Veritas Hall D411, 21983, Incheon, KOREA, REPUBLIC OF.
Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by the deposition of amyloid-β (Aβ) peptides, which aggregate into toxic structures such as oligomers, fibrils, and plaques. The presence of these Aβ aggregates in the brain plays a crucial role in the pathophysiology, leading to synaptic dysfunction and cognitive impairment. Understanding how physiological factors affect Aβ aggregation is essential, and therefore, exploring their influence in vitro will likely provide insights into their role in AD pathology.
View Article and Find Full Text PDFSelenium ameliorates cognitive impairment through activating BDNF/TrkB pathway.
J Trace Elem Med Biol
January 2025
Department of Epidemiology and Health Statistics, School of Public Health, Ningxia Medical University, Yinchuan 750004, China; Key Laboratory of Environmental Factors and Chronic Disease Control, Yinchuan 750004, China. Electronic address:
Background: Alzheimer's disease (AD) is a neurodegenerative disorder that primarily affects older adults. Selenium, an essential micronutrient for humans, plays a crucial role in the body's normal physiological and metabolic processes. A long-term deficiency in selenium intake can lead to various diseases and even contribute to the ageing process.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!