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Altered levels of acetylcholinesterase in Alzheimer plasma
Many 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 succes...
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Published in: | PloS one 2010-01, Vol.5 (1), p.e8701-e8701 |
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description | Many 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.
Here 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 approximately 20 nmol/min/mL, about 160 times lower than BuChE. The majority of AChE species are the light G(1)+G(2) forms and not G(4) 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 G(1)+G(2) 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.
Plasma AChE might have potential as an indicator of disease progress and prognosis in AD and warrants further investigation. |
doi_str_mv | 10.1371/journal.pone.0008701 |
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Here 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 approximately 20 nmol/min/mL, about 160 times lower than BuChE. The majority of AChE species are the light G(1)+G(2) forms and not G(4) 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 G(1)+G(2) 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.
Plasma AChE might have potential as an indicator of disease progress and prognosis in AD and warrants further investigation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0008701</identifier><identifier>PMID: 20090844</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acetylcholinesterase ; Acetylcholinesterase - blood ; Aged ; Aging ; Alzheimer Disease - blood ; Alzheimer's disease ; Alzheimers disease ; Analysis ; Apoptosis ; Biochemistry ; Biochemistry/Protein Chemistry ; Blood ; Blood cells ; Blood plasma ; Blood-brain barrier ; Blotting, Western ; Brain ; Case-Control Studies ; Cerebrospinal fluid ; Cholinesterase ; Cholinesterase inhibitors ; Chromatography ; Dementia ; Disease control ; Enzymes ; Erythrocyte sedimentation rate ; Erythrocytes ; Female ; Hepatocytes ; Humans ; Immunoassay ; Immunoglobulins ; Lectins ; Light levels ; Liver ; Male ; Neurodegenerative diseases ; Neurological Disorders/Alzheimer Disease ; Plasmas (physics) ; Proteins ; Red blood cells ; Sedimentation ; Western blotting</subject><ispartof>PloS one, 2010-01, Vol.5 (1), p.e8701-e8701</ispartof><rights>COPYRIGHT 2010 Public Library of Science</rights><rights>2010 García-Ayllón et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>García-Ayllón et al. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c723t-a32e12c711427a81a84c792ee6cf456e46c01d5cd87ac87af5d2c7ea19bb8083</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1289252092/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1289252092?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20090844$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Kursula, Petri</contributor><creatorcontrib>García-Ayllón, María-Salud</creatorcontrib><creatorcontrib>Riba-Llena, Iolanda</creatorcontrib><creatorcontrib>Serra-Basante, Carol</creatorcontrib><creatorcontrib>Alom, Jordi</creatorcontrib><creatorcontrib>Boopathy, Rathnam</creatorcontrib><creatorcontrib>Sáez-Valero, Javier</creatorcontrib><title>Altered levels of acetylcholinesterase in Alzheimer plasma</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Many 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.
Here 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 approximately 20 nmol/min/mL, about 160 times lower than BuChE. The majority of AChE species are the light G(1)+G(2) forms and not G(4) 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 G(1)+G(2) 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.
Plasma AChE might have potential as an indicator of disease progress and prognosis in AD and warrants further investigation.</description><subject>Acetylcholinesterase</subject><subject>Acetylcholinesterase - blood</subject><subject>Aged</subject><subject>Aging</subject><subject>Alzheimer Disease - blood</subject><subject>Alzheimer's disease</subject><subject>Alzheimers disease</subject><subject>Analysis</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Biochemistry/Protein Chemistry</subject><subject>Blood</subject><subject>Blood cells</subject><subject>Blood plasma</subject><subject>Blood-brain barrier</subject><subject>Blotting, Western</subject><subject>Brain</subject><subject>Case-Control Studies</subject><subject>Cerebrospinal fluid</subject><subject>Cholinesterase</subject><subject>Cholinesterase inhibitors</subject><subject>Chromatography</subject><subject>Dementia</subject><subject>Disease control</subject><subject>Enzymes</subject><subject>Erythrocyte sedimentation rate</subject><subject>Erythrocytes</subject><subject>Female</subject><subject>Hepatocytes</subject><subject>Humans</subject><subject>Immunoassay</subject><subject>Immunoglobulins</subject><subject>Lectins</subject><subject>Light levels</subject><subject>Liver</subject><subject>Male</subject><subject>Neurodegenerative diseases</subject><subject>Neurological Disorders/Alzheimer Disease</subject><subject>Plasmas (physics)</subject><subject>Proteins</subject><subject>Red blood cells</subject><subject>Sedimentation</subject><subject>Western blotting</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNk22L1DAQx4so3nn6DUQLguKLXfPUJvWFsBw-LBwc6OHbME2nu1nSZm3aw_PTm7q9YysHSggJk9_8JzPJJMlzSpaUS_pu54euBbfc-xaXhBAlCX2QnNKCs0XOCH94tD9JnoSwIyTjKs8fJyeMkIIoIU6T9yvXY4dV6vAaXUh9nYLB_saZrXe2xRBPIWBq23Tlfm3RNtilewehgafJoxpcwGfTepZcffp4df5lcXH5eX2-ulgYyXi_AM6QMiMpFUyCoqCEkQVDzE0tshxFbgitMlMpCSbOOqsijUCLslRE8bPk5UF273zQU9ZBU6YKljFSsEisD0TlYaf3nW2gu9EerP5j8N1GQ9db41AbUWamlFVZKCNQEcih5ogmGiqWyzHahynaUDZYGWz7DtxMdH7S2q3e-GvNFMkVE1HgzSTQ-R9DrJ9ubDDoHLToh6ClyCQpVEH-TXKeCc7kqPnqL_L-MkzUBmKmtq19vKAZNfVKSF4wkmdj1OU9VBwVNtbEv1TbaJ85vJ05RKbHn_0GhhD0-tvX_2cvv8_Z10fsFsH12-Dd0FvfhjkoDqDpfAgd1nevQYkeW-G2GnpsBT21QnR7cfySd063f5__BrMrAzU</recordid><startdate>20100114</startdate><enddate>20100114</enddate><creator>García-Ayllón, María-Salud</creator><creator>Riba-Llena, Iolanda</creator><creator>Serra-Basante, Carol</creator><creator>Alom, Jordi</creator><creator>Boopathy, Rathnam</creator><creator>Sáez-Valero, Javier</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>7TK</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20100114</creationdate><title>Altered levels of acetylcholinesterase in Alzheimer plasma</title><author>García-Ayllón, María-Salud ; Riba-Llena, Iolanda ; Serra-Basante, Carol ; Alom, Jordi ; Boopathy, Rathnam ; Sáez-Valero, Javier</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c723t-a32e12c711427a81a84c792ee6cf456e46c01d5cd87ac87af5d2c7ea19bb8083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Acetylcholinesterase</topic><topic>Acetylcholinesterase - blood</topic><topic>Aged</topic><topic>Aging</topic><topic>Alzheimer Disease - blood</topic><topic>Alzheimer's disease</topic><topic>Alzheimers disease</topic><topic>Analysis</topic><topic>Apoptosis</topic><topic>Biochemistry</topic><topic>Biochemistry/Protein Chemistry</topic><topic>Blood</topic><topic>Blood cells</topic><topic>Blood plasma</topic><topic>Blood-brain barrier</topic><topic>Blotting, Western</topic><topic>Brain</topic><topic>Case-Control Studies</topic><topic>Cerebrospinal fluid</topic><topic>Cholinesterase</topic><topic>Cholinesterase inhibitors</topic><topic>Chromatography</topic><topic>Dementia</topic><topic>Disease control</topic><topic>Enzymes</topic><topic>Erythrocyte sedimentation rate</topic><topic>Erythrocytes</topic><topic>Female</topic><topic>Hepatocytes</topic><topic>Humans</topic><topic>Immunoassay</topic><topic>Immunoglobulins</topic><topic>Lectins</topic><topic>Light levels</topic><topic>Liver</topic><topic>Male</topic><topic>Neurodegenerative diseases</topic><topic>Neurological Disorders/Alzheimer Disease</topic><topic>Plasmas (physics)</topic><topic>Proteins</topic><topic>Red blood cells</topic><topic>Sedimentation</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>García-Ayllón, María-Salud</creatorcontrib><creatorcontrib>Riba-Llena, Iolanda</creatorcontrib><creatorcontrib>Serra-Basante, Carol</creatorcontrib><creatorcontrib>Alom, Jordi</creatorcontrib><creatorcontrib>Boopathy, Rathnam</creatorcontrib><creatorcontrib>Sáez-Valero, Javier</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database (ProQuest)</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database (Proquest)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>García-Ayllón, María-Salud</au><au>Riba-Llena, Iolanda</au><au>Serra-Basante, Carol</au><au>Alom, Jordi</au><au>Boopathy, Rathnam</au><au>Sáez-Valero, Javier</au><au>Kursula, Petri</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Altered levels of acetylcholinesterase in Alzheimer plasma</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2010-01-14</date><risdate>2010</risdate><volume>5</volume><issue>1</issue><spage>e8701</spage><epage>e8701</epage><pages>e8701-e8701</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Many 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.
Here 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 approximately 20 nmol/min/mL, about 160 times lower than BuChE. The majority of AChE species are the light G(1)+G(2) forms and not G(4) 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 G(1)+G(2) 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.
Plasma AChE might have potential as an indicator of disease progress and prognosis in AD and warrants further investigation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>20090844</pmid><doi>10.1371/journal.pone.0008701</doi><tpages>e8701</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Acetylcholinesterase Acetylcholinesterase - blood Aged Aging Alzheimer Disease - blood Alzheimer's disease Alzheimers disease Analysis Apoptosis Biochemistry Biochemistry/Protein Chemistry Blood Blood cells Blood plasma Blood-brain barrier Blotting, Western Brain Case-Control Studies Cerebrospinal fluid Cholinesterase Cholinesterase inhibitors Chromatography Dementia Disease control Enzymes Erythrocyte sedimentation rate Erythrocytes Female Hepatocytes Humans Immunoassay Immunoglobulins Lectins Light levels Liver Male Neurodegenerative diseases Neurological Disorders/Alzheimer Disease Plasmas (physics) Proteins Red blood cells Sedimentation Western blotting |
title | Altered levels of acetylcholinesterase in Alzheimer plasma |
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