Effects of CD2-associated protein deficiency on amyloid-β in neuroblastoma cells and in an APP transgenic mouse model
CD2-associated protein (CD2AP) is an SH3-containing scaffold adaptor protein which regulates the actin cytoskeleton. Recently, CD2AP was identified as a genetic risk factor for Alzheimer's disease (AD) by several genome-wide association studies. One of the hallmarks of AD is the accumulation of...
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| Veröffentlicht in: | Molecular neurodegeneration 2015-03, Vol.10 (1), p.12-12, Article 12 |
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| creator | Liao, Fan Jiang, Hong Srivatsan, Subhashini Xiao, Qingli Lefton, Katheryn B Yamada, Kaoru Mahan, Thomas E Lee, Jin-Moo Shaw, Andrey S Holtzman, David M |
| description | CD2-associated protein (CD2AP) is an SH3-containing scaffold adaptor protein which regulates the actin cytoskeleton. Recently, CD2AP was identified as a genetic risk factor for Alzheimer's disease (AD) by several genome-wide association studies. One of the hallmarks of AD is the accumulation of aggregated forms of Amyloid-β (Aβ) in the brain. In humans, CD2AP AD susceptibility locus (rs9349407) is associated with an increased plaque burden. Aβ production is highly regulated by endocytosis and is influenced by lysosomal function. Lysosomal trafficking is influenced by CD2AP. In this study, we decreased CD2AP levels in N2a neuroblastoma cultures and PS1APP mice and analyzed Aβ levels and plaque burden.
Our data show that suppressing CD2AP expression using shRNA in N2a-APP695 cells results in decreased cell membrane amyloid precursor protein, decreased Aβ release and a lower Aβ42/Aβ40 ratio. CD2AP protein is expressed in the brain as detected by western blot, and the expression level is dependent on gene dosage. In 1-month old PS1APP mice, complete loss of CD2AP in brain resulted in a decreased Aβ42/Aβ40 ratio in brain tissue lysates while there was no effect on Aβ deposition or accumulation in PS1APP mice expressing one copy of CD2AP.
CD2-Associated Protein affects Aβ levels and Aβ42/Aβ40 ratio in vitro. The effect of CD2-Associated Protein on Aβ metabolism is subtle in vivo. |
| doi_str_mv | 10.1186/s13024-015-0006-y |
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Our data show that suppressing CD2AP expression using shRNA in N2a-APP695 cells results in decreased cell membrane amyloid precursor protein, decreased Aβ release and a lower Aβ42/Aβ40 ratio. CD2AP protein is expressed in the brain as detected by western blot, and the expression level is dependent on gene dosage. In 1-month old PS1APP mice, complete loss of CD2AP in brain resulted in a decreased Aβ42/Aβ40 ratio in brain tissue lysates while there was no effect on Aβ deposition or accumulation in PS1APP mice expressing one copy of CD2AP.
CD2-Associated Protein affects Aβ levels and Aβ42/Aβ40 ratio in vitro. The effect of CD2-Associated Protein on Aβ metabolism is subtle in vivo.</description><identifier>ISSN: 1750-1326</identifier><identifier>EISSN: 1750-1326</identifier><identifier>DOI: 10.1186/s13024-015-0006-y</identifier><identifier>PMID: 25887956</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Adaptor Proteins, Signal Transducing - deficiency ; Adaptor Proteins, Signal Transducing - metabolism ; Alzheimer Disease - genetics ; Alzheimer Disease - metabolism ; Amyloid beta-Peptides - genetics ; Amyloid beta-Peptides - metabolism ; Amyloid beta-Protein Precursor - genetics ; Amyloid beta-Protein Precursor - metabolism ; Amyloid Precursor Protein Secretases - metabolism ; Animals ; Brain - metabolism ; Cytoskeletal Proteins - deficiency ; Cytoskeletal Proteins - metabolism ; Disease Models, Animal ; Genome-Wide Association Study ; Humans ; Mice, Transgenic ; Neuroblastoma - genetics ; Neuroblastoma - metabolism</subject><ispartof>Molecular neurodegeneration, 2015-03, Vol.10 (1), p.12-12, Article 12</ispartof><rights>Liao et al.; licensee BioMed Central. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b460t-3f7602ce64f74441fa1c6b6c2a8597d234018929ee1a98b3ef63d316e1afbe43</citedby><cites>FETCH-LOGICAL-b460t-3f7602ce64f74441fa1c6b6c2a8597d234018929ee1a98b3ef63d316e1afbe43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374406/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374406/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25887956$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liao, Fan</creatorcontrib><creatorcontrib>Jiang, Hong</creatorcontrib><creatorcontrib>Srivatsan, Subhashini</creatorcontrib><creatorcontrib>Xiao, Qingli</creatorcontrib><creatorcontrib>Lefton, Katheryn B</creatorcontrib><creatorcontrib>Yamada, Kaoru</creatorcontrib><creatorcontrib>Mahan, Thomas E</creatorcontrib><creatorcontrib>Lee, Jin-Moo</creatorcontrib><creatorcontrib>Shaw, Andrey S</creatorcontrib><creatorcontrib>Holtzman, David M</creatorcontrib><title>Effects of CD2-associated protein deficiency on amyloid-β in neuroblastoma cells and in an APP transgenic mouse model</title><title>Molecular neurodegeneration</title><addtitle>Mol Neurodegener</addtitle><description>CD2-associated protein (CD2AP) is an SH3-containing scaffold adaptor protein which regulates the actin cytoskeleton. Recently, CD2AP was identified as a genetic risk factor for Alzheimer's disease (AD) by several genome-wide association studies. One of the hallmarks of AD is the accumulation of aggregated forms of Amyloid-β (Aβ) in the brain. In humans, CD2AP AD susceptibility locus (rs9349407) is associated with an increased plaque burden. Aβ production is highly regulated by endocytosis and is influenced by lysosomal function. Lysosomal trafficking is influenced by CD2AP. In this study, we decreased CD2AP levels in N2a neuroblastoma cultures and PS1APP mice and analyzed Aβ levels and plaque burden.
Our data show that suppressing CD2AP expression using shRNA in N2a-APP695 cells results in decreased cell membrane amyloid precursor protein, decreased Aβ release and a lower Aβ42/Aβ40 ratio. CD2AP protein is expressed in the brain as detected by western blot, and the expression level is dependent on gene dosage. In 1-month old PS1APP mice, complete loss of CD2AP in brain resulted in a decreased Aβ42/Aβ40 ratio in brain tissue lysates while there was no effect on Aβ deposition or accumulation in PS1APP mice expressing one copy of CD2AP.
CD2-Associated Protein affects Aβ levels and Aβ42/Aβ40 ratio in vitro. The effect of CD2-Associated Protein on Aβ metabolism is subtle in vivo.</description><subject>Adaptor Proteins, Signal Transducing - deficiency</subject><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Alzheimer Disease - genetics</subject><subject>Alzheimer Disease - metabolism</subject><subject>Amyloid beta-Peptides - genetics</subject><subject>Amyloid beta-Peptides - metabolism</subject><subject>Amyloid beta-Protein Precursor - genetics</subject><subject>Amyloid beta-Protein Precursor - metabolism</subject><subject>Amyloid Precursor Protein Secretases - metabolism</subject><subject>Animals</subject><subject>Brain - metabolism</subject><subject>Cytoskeletal Proteins - deficiency</subject><subject>Cytoskeletal Proteins - metabolism</subject><subject>Disease Models, Animal</subject><subject>Genome-Wide Association Study</subject><subject>Humans</subject><subject>Mice, Transgenic</subject><subject>Neuroblastoma - genetics</subject><subject>Neuroblastoma - metabolism</subject><issn>1750-1326</issn><issn>1750-1326</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kctKxTAQhoMo3h_AjWTpJppb03YjyPEKgi7chzSdaKRNjk2P0NfyQXwmczgqCrrJJPwz30zmR-iA0WPGKnWSmKBcEsoKQilVZFpD26wsKGGCq_Uf9y20k9IzpbKktNhEW7yoqrIu1DZ6vXAO7JhwdHh2zolJKVpvRmjxfIgj-IBbcN56CHbCMWDTT130LXl_w1kLsBhi05k0xt5gC12XsAntUjIBn93f43EwIT1C8Bb3cZEgny10e2jDmS7B_mfcRQ-XFw-za3J7d3UzO7sljVR0JMKVinILSrpSSsmcYVY1ynJTFXXZciEpq2peAzBTV40Ap0QrmMpP14AUu-h0hZ0vmh5aCyGP0-n54HszTDoar38rwT_px_iqpcj9qMqA8xWg8fEfwG_Fxl6vbNHZFr20RU8Zc_Q5xxBfFpBG3fu03JYJkJeimSqlqkrJRU5lq1Q7xJQGcN_NGNVL1__EH_785nfFl83iAyFJrAU</recordid><startdate>20150319</startdate><enddate>20150319</enddate><creator>Liao, Fan</creator><creator>Jiang, Hong</creator><creator>Srivatsan, Subhashini</creator><creator>Xiao, Qingli</creator><creator>Lefton, Katheryn B</creator><creator>Yamada, Kaoru</creator><creator>Mahan, Thomas E</creator><creator>Lee, Jin-Moo</creator><creator>Shaw, Andrey S</creator><creator>Holtzman, David M</creator><general>BioMed Central Ltd</general><general>BioMed Central</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150319</creationdate><title>Effects of CD2-associated protein deficiency on amyloid-β in neuroblastoma cells and in an APP transgenic mouse model</title><author>Liao, Fan ; Jiang, Hong ; Srivatsan, Subhashini ; Xiao, Qingli ; Lefton, Katheryn B ; Yamada, Kaoru ; Mahan, Thomas E ; Lee, Jin-Moo ; Shaw, Andrey S ; Holtzman, David M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b460t-3f7602ce64f74441fa1c6b6c2a8597d234018929ee1a98b3ef63d316e1afbe43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adaptor Proteins, Signal Transducing - deficiency</topic><topic>Adaptor Proteins, Signal Transducing - metabolism</topic><topic>Alzheimer Disease - genetics</topic><topic>Alzheimer Disease - metabolism</topic><topic>Amyloid beta-Peptides - genetics</topic><topic>Amyloid beta-Peptides - metabolism</topic><topic>Amyloid beta-Protein Precursor - genetics</topic><topic>Amyloid beta-Protein Precursor - metabolism</topic><topic>Amyloid Precursor Protein Secretases - metabolism</topic><topic>Animals</topic><topic>Brain - metabolism</topic><topic>Cytoskeletal Proteins - deficiency</topic><topic>Cytoskeletal Proteins - metabolism</topic><topic>Disease Models, Animal</topic><topic>Genome-Wide Association Study</topic><topic>Humans</topic><topic>Mice, Transgenic</topic><topic>Neuroblastoma - genetics</topic><topic>Neuroblastoma - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liao, Fan</creatorcontrib><creatorcontrib>Jiang, Hong</creatorcontrib><creatorcontrib>Srivatsan, Subhashini</creatorcontrib><creatorcontrib>Xiao, Qingli</creatorcontrib><creatorcontrib>Lefton, Katheryn B</creatorcontrib><creatorcontrib>Yamada, Kaoru</creatorcontrib><creatorcontrib>Mahan, Thomas E</creatorcontrib><creatorcontrib>Lee, Jin-Moo</creatorcontrib><creatorcontrib>Shaw, Andrey S</creatorcontrib><creatorcontrib>Holtzman, David M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular neurodegeneration</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liao, Fan</au><au>Jiang, Hong</au><au>Srivatsan, Subhashini</au><au>Xiao, Qingli</au><au>Lefton, Katheryn B</au><au>Yamada, Kaoru</au><au>Mahan, Thomas E</au><au>Lee, Jin-Moo</au><au>Shaw, Andrey S</au><au>Holtzman, David M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of CD2-associated protein deficiency on amyloid-β in neuroblastoma cells and in an APP transgenic mouse model</atitle><jtitle>Molecular neurodegeneration</jtitle><addtitle>Mol Neurodegener</addtitle><date>2015-03-19</date><risdate>2015</risdate><volume>10</volume><issue>1</issue><spage>12</spage><epage>12</epage><pages>12-12</pages><artnum>12</artnum><issn>1750-1326</issn><eissn>1750-1326</eissn><abstract>CD2-associated protein (CD2AP) is an SH3-containing scaffold adaptor protein which regulates the actin cytoskeleton. Recently, CD2AP was identified as a genetic risk factor for Alzheimer's disease (AD) by several genome-wide association studies. One of the hallmarks of AD is the accumulation of aggregated forms of Amyloid-β (Aβ) in the brain. In humans, CD2AP AD susceptibility locus (rs9349407) is associated with an increased plaque burden. Aβ production is highly regulated by endocytosis and is influenced by lysosomal function. Lysosomal trafficking is influenced by CD2AP. In this study, we decreased CD2AP levels in N2a neuroblastoma cultures and PS1APP mice and analyzed Aβ levels and plaque burden.
Our data show that suppressing CD2AP expression using shRNA in N2a-APP695 cells results in decreased cell membrane amyloid precursor protein, decreased Aβ release and a lower Aβ42/Aβ40 ratio. CD2AP protein is expressed in the brain as detected by western blot, and the expression level is dependent on gene dosage. In 1-month old PS1APP mice, complete loss of CD2AP in brain resulted in a decreased Aβ42/Aβ40 ratio in brain tissue lysates while there was no effect on Aβ deposition or accumulation in PS1APP mice expressing one copy of CD2AP.
CD2-Associated Protein affects Aβ levels and Aβ42/Aβ40 ratio in vitro. The effect of CD2-Associated Protein on Aβ metabolism is subtle in vivo.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>25887956</pmid><doi>10.1186/s13024-015-0006-y</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adaptor Proteins, Signal Transducing - deficiency Adaptor Proteins, Signal Transducing - metabolism Alzheimer Disease - genetics Alzheimer Disease - metabolism Amyloid beta-Peptides - genetics Amyloid beta-Peptides - metabolism Amyloid beta-Protein Precursor - genetics Amyloid beta-Protein Precursor - metabolism Amyloid Precursor Protein Secretases - metabolism Animals Brain - metabolism Cytoskeletal Proteins - deficiency Cytoskeletal Proteins - metabolism Disease Models, Animal Genome-Wide Association Study Humans Mice, Transgenic Neuroblastoma - genetics Neuroblastoma - metabolism |
| title | Effects of CD2-associated protein deficiency on amyloid-β in neuroblastoma cells and in an APP transgenic mouse model |
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