Deglycosylated anti-Abeta antibody dose-response effects on pathology and memory in APP transgenic mice
Anti-Abeta antibody administration to amyloid-depositing transgenic mice can reverse amyloid pathology and restore memory function. However, in old mice, these treatments also increase vascular leakage and promote formation of vascular amyloid deposits. Deglycosylated antibodies with reduced affinit...
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| Veröffentlicht in: | Journal of neuroimmune pharmacology 2008-09, Vol.3 (3), p.187-197 |
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| container_title | Journal of neuroimmune pharmacology |
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| creator | Karlnoski, Rachel A Rosenthal, Arnon Alamed, Jennifer Ronan, Victoria Gordon, Marcia N Gottschall, Paul E Grimm, Jan Pons, Jaume Morgan, Dave |
| description | Anti-Abeta antibody administration to amyloid-depositing transgenic mice can reverse amyloid pathology and restore memory function. However, in old mice, these treatments also increase vascular leakage and promote formation of vascular amyloid deposits. Deglycosylated antibodies with reduced affinity for Fcgamma receptors and complement are associated with reduced vascular amyloid and microhemorrhage while retaining amyloid-clearing and memory-enhancing properties of native intact antibodies. In the current experiment, we investigated the effect of 3, 10, or 30 mg/kg of deglycosylated antibody (D-2H6) on amyloid pathology and cognitive behavior in old Tg2576 mice. We found that low doses of deglycosylated antibody appear more efficacious than higher doses in reducing pathology and memory loss in amyloid precursor protein (APP) transgenic mice. These data suggest that excess antibody unbound to antigen can interfere with antibody-mediated Abeta clearance, possibly by saturating the FcRn antibody transporter. |
| doi_str_mv | 10.1007/s11481-008-9114-6 |
| format | Article |
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However, in old mice, these treatments also increase vascular leakage and promote formation of vascular amyloid deposits. Deglycosylated antibodies with reduced affinity for Fcgamma receptors and complement are associated with reduced vascular amyloid and microhemorrhage while retaining amyloid-clearing and memory-enhancing properties of native intact antibodies. In the current experiment, we investigated the effect of 3, 10, or 30 mg/kg of deglycosylated antibody (D-2H6) on amyloid pathology and cognitive behavior in old Tg2576 mice. We found that low doses of deglycosylated antibody appear more efficacious than higher doses in reducing pathology and memory loss in amyloid precursor protein (APP) transgenic mice. 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These data suggest that excess antibody unbound to antigen can interfere with antibody-mediated Abeta clearance, possibly by saturating the FcRn antibody transporter.</description><subject>Aging - genetics</subject><subject>Amyloid - antagonists & inhibitors</subject><subject>Amyloid - metabolism</subject><subject>Amyloid beta-Peptides - immunology</subject><subject>Amyloid beta-Peptides - metabolism</subject><subject>Amyloid beta-Protein Precursor - genetics</subject><subject>Animals</subject><subject>Antibodies - administration & dosage</subject><subject>Antibodies - metabolism</subject><subject>Brain - metabolism</subject><subject>Brain - pathology</subject><subject>Dose-Response Relationship, Immunologic</subject><subject>Glycosylation</subject><subject>Memory - physiology</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><issn>1557-1904</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kLFOwzAURS0kREvhA1iQJzaDXTuxM1aFAlIlOnSPXuyXEJTYIXaH_D0RlOke6R7d4RJyJ_ij4Fw_RSGUEYxzw4oZWX5BliLLNBMFVwtyHeMX50opzq_IQpica52ZJWmesekmG-LUQUJHwaeWbSpM8ItVcBN1ISIbMQ7BR6RY12hTpMHTAdJn6EIzza6jPfZhnGjr6eZwoGkEHxv0raV9a_GGXNbQRbw954ocdy_H7Rvbf7y-bzd7NmTKsLV0dWWcK8CCLGS15hwtOGk1KBTWGRT53PACclXDupaVMaCVzBxoYTXKFXn4mx3G8H3CmMq-jRa7DjyGUyzzQok8y_Us3p_FU9WjK4ex7WGcyv9n5A-C8mYu</recordid><startdate>200809</startdate><enddate>200809</enddate><creator>Karlnoski, Rachel A</creator><creator>Rosenthal, Arnon</creator><creator>Alamed, Jennifer</creator><creator>Ronan, Victoria</creator><creator>Gordon, Marcia N</creator><creator>Gottschall, Paul E</creator><creator>Grimm, Jan</creator><creator>Pons, Jaume</creator><creator>Morgan, Dave</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>200809</creationdate><title>Deglycosylated anti-Abeta antibody dose-response effects on pathology and memory in APP transgenic mice</title><author>Karlnoski, Rachel A ; Rosenthal, Arnon ; Alamed, Jennifer ; Ronan, Victoria ; Gordon, Marcia N ; Gottschall, Paul E ; Grimm, Jan ; Pons, Jaume ; Morgan, Dave</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p548-23dfb8dd9aca393b200ecad3c7a4e1cd8e16ca309a64fa2f3b88a7435da71c7e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Aging - genetics</topic><topic>Amyloid - antagonists & inhibitors</topic><topic>Amyloid - metabolism</topic><topic>Amyloid beta-Peptides - immunology</topic><topic>Amyloid beta-Peptides - metabolism</topic><topic>Amyloid beta-Protein Precursor - genetics</topic><topic>Animals</topic><topic>Antibodies - administration & dosage</topic><topic>Antibodies - metabolism</topic><topic>Brain - metabolism</topic><topic>Brain - pathology</topic><topic>Dose-Response Relationship, Immunologic</topic><topic>Glycosylation</topic><topic>Memory - physiology</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Karlnoski, Rachel A</creatorcontrib><creatorcontrib>Rosenthal, Arnon</creatorcontrib><creatorcontrib>Alamed, Jennifer</creatorcontrib><creatorcontrib>Ronan, Victoria</creatorcontrib><creatorcontrib>Gordon, Marcia N</creatorcontrib><creatorcontrib>Gottschall, Paul E</creatorcontrib><creatorcontrib>Grimm, Jan</creatorcontrib><creatorcontrib>Pons, Jaume</creatorcontrib><creatorcontrib>Morgan, Dave</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neuroimmune pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Karlnoski, Rachel A</au><au>Rosenthal, Arnon</au><au>Alamed, Jennifer</au><au>Ronan, Victoria</au><au>Gordon, Marcia N</au><au>Gottschall, Paul E</au><au>Grimm, Jan</au><au>Pons, Jaume</au><au>Morgan, Dave</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Deglycosylated anti-Abeta antibody dose-response effects on pathology and memory in APP transgenic mice</atitle><jtitle>Journal of neuroimmune pharmacology</jtitle><addtitle>J Neuroimmune Pharmacol</addtitle><date>2008-09</date><risdate>2008</risdate><volume>3</volume><issue>3</issue><spage>187</spage><epage>197</epage><pages>187-197</pages><eissn>1557-1904</eissn><abstract>Anti-Abeta antibody administration to amyloid-depositing transgenic mice can reverse amyloid pathology and restore memory function. 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| ispartof | Journal of neuroimmune pharmacology, 2008-09, Vol.3 (3), p.187-197 |
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| language | eng |
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| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Aging - genetics Amyloid - antagonists & inhibitors Amyloid - metabolism Amyloid beta-Peptides - immunology Amyloid beta-Peptides - metabolism Amyloid beta-Protein Precursor - genetics Animals Antibodies - administration & dosage Antibodies - metabolism Brain - metabolism Brain - pathology Dose-Response Relationship, Immunologic Glycosylation Memory - physiology Mice Mice, Transgenic |
| title | Deglycosylated anti-Abeta antibody dose-response effects on pathology and memory in APP transgenic mice |
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