Abstract
BackgroundMany studies have been conducted in an extensive effort to identify alterations in blood cholinesterase levels as a consequence of disease, including the analysis of acetylcholinesterase (AChE) in plasma. Conventional assays using selective cholinesterase inhibitors have not been particularly successful as excess amounts of butyrylcholinesterase (BuChE) pose a major problem.Principal FindingsHere we have estimated the levels of AChE activity in human plasma by first immunoprecipitating BuChE and measuring AChE activity in the immunodepleted plasma. Human plasma AChE activity levels were ∼20 nmol/min/mL, about 160 times lower than BuChE. The majority of AChE species are the light G1+G2 forms and not G4 tetramers. The levels and pattern of the molecular forms are similar to that observed in individuals with silent BuChE. We have also compared plasma AChE with the enzyme pattern obtained from human liver, red blood cells, cerebrospinal fluid (CSF) and brain, by sedimentation analysis, Western blotting and lectin-binding analysis. Finally, a selective increase of AChE activity was detected in plasma from Alzheimer's disease (AD) patients compared to age and gender-matched controls. This increase correlates with an increase in the G1+G2 forms, the subset of AChE species which are increased in Alzheimer's brain. Western blot analysis demonstrated that a 78 kDa immunoreactive AChE protein band was also increased in Alzheimer's plasma, attributed in part to AChE-T subunits common in brain and CSF.ConclusionPlasma AChE might have potential as an indicator of disease progress and prognosis in AD and warrants further investigation.
Highlights
Alzheimer’s disease (AD) is the leading cause of dementia in the aged population
Plasma AChE might have potential as an indicator of disease progress and prognosis in AD and warrants further investigation
As the elevated levels of BuChE in human plasma were expected to interfere in the determination of AChE, two cycles of BuChE immunoprecipitation were first performed in plasma aliquots from healthy individuals (4664 years)
Summary
Alzheimer’s disease (AD) is the leading cause of dementia in the aged population. The main neuropathological changes associated with AD are b-amyloid plaque accumulation, neurofibrillary tangle formation and substantial synaptic and neuronal loss in critical brain areas. Acetylcholinesterase (EC 3.1.1.7; AChE), the enzyme responsible for the inactivation of cholinergic neurotransmission, is consistently decreased in the AD brain [1,2] Despite this overall decrease, levels of AChE are increased around b-amyloid plaques [3,4] and it has been proposed that AChE may play a role in b-amyloid fibrillogenesis [5,6]. Levels of AChE are increased around b-amyloid plaques [3,4] and it has been proposed that AChE may play a role in b-amyloid fibrillogenesis [5,6] In this context, the altered expression pattern of AChE species in the AD brain is of particular interest. Conventional assays using selective cholinesterase inhibitors have not been successful as excess amounts of butyrylcholinesterase (BuChE) pose a major problem
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
