Epistasis between tau phosphorylation regulating genes (CDK5R1 and GSK-3β) and Alzheimer's disease risk
Objective – Glycogen synthase kinase‐3β (GSK‐3β) and cyclin‐dependent kinase 5 (CDK5) have been implicated as two major protein kinases involved in the abnormal hyperphosphorylation of tau in Alzheimer’s disease (AD) brain, and the development of neurofibrillary tangles. CDK5 regulatory subunit 1 (...
Gespeichert in:
| Veröffentlicht in: | Acta neurologica Scandinavica 2009-08, Vol.120 (2), p.130-133 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 133 |
|---|---|
| container_issue | 2 |
| container_start_page | 130 |
| container_title | Acta neurologica Scandinavica |
| container_volume | 120 |
| creator | Mateo, I. Vázquez-Higuera, J. L. Sánchez-Juan, P. Rodríguez-Rodríguez, E. Infante, J. García-Gorostiaga, I. Berciano, J. Combarros, O. |
| description | Objective – Glycogen synthase kinase‐3β (GSK‐3β) and cyclin‐dependent kinase 5 (CDK5) have been implicated as two major protein kinases involved in the abnormal hyperphosphorylation of tau in Alzheimer’s disease (AD) brain, and the development of neurofibrillary tangles. CDK5 regulatory subunit 1 (CDK5R1) encodes for p35, a protein required for activation of CDK5. As both CDK5R1 and GSK‐3β genes are related to phosphorylation of tau, we examined the combined contribution of these genes to the susceptibility for AD.
Methods – In a case–control study in 283 AD patients and 263 healthy controls, we examined the combined effects between CDK5R1 (3′‐UTR, rs735555) and GSK‐3β (−50, rs334558) polymorphisms on susceptibility to AD.
Results – Subjects carrying both the CDK5R1 (3′‐UTR, rs735555) AA genotype and the GSK‐3β (−50, rs334558) CC genotype had a 12.5‐fold decrease in AD risk (adjusted by age, sex and APOE status OR = 0.08, 95% CI = 0.01–0.76, P = 0.03), suggesting synergistic effects (epistasis) between both genes.
Conclusion – These data support a role for tau phosphorylation regulating genes in risk for AD. |
| doi_str_mv | 10.1111/j.1600-0404.2008.01128.x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67509869</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>20221684</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5168-f4860a09c833d19ab17f3c9bf6aa161633aad488066dfcea8ff321435a6686dd3</originalsourceid><addsrcrecordid>eNqNkc2O0zAUhS0EYsrAKyBv-Fsk2LHjOAsWVSgFzWiQ-BuJjXWb3LTupEmxE03LY_EgPBPOtCpLsGT5Xvk79tU5hFDOYh7W63XMFWMRk0zGCWM6ZpwnOt7dI5PTxX0yYYzxSAkuz8gj79ehSzIpH5IznvNUpiKbkNVsa30P3nq6wP4WsaU9DHS76nzYbt9Ab7uWOlwOY9ku6RJb9PRl8fYi_cQptBWdf76IxO9fr-6aafNzhXaD7oWnlfUIHqmz_uYxeVBD4_HJ8TwnX9_NvhTvo8uP8w_F9DIqU650VEutGLC81EJUPIcFz2pR5otaAXDFlRAAldSaKVXVJYKua5FwKVJQSquqEufk-eHdret-DOh7s7G-xKaBFrvBG5WlLNcq_yeYsCQJE8kA6gNYus57h7XZOrsBtzecmTEOszaj62Z03YxxmLs4zC5Inx7_GBYbrP4Kj_4H4NkRAF9CUztoS-tPXBgg51rzwL05cLe2wf1_D2CmV7OxCvrooA9h4-6kB3cTDBFZaq6v5iZn35PrIivMN_EHTte0LQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>20221684</pqid></control><display><type>article</type><title>Epistasis between tau phosphorylation regulating genes (CDK5R1 and GSK-3β) and Alzheimer's disease risk</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Mateo, I. ; Vázquez-Higuera, J. L. ; Sánchez-Juan, P. ; Rodríguez-Rodríguez, E. ; Infante, J. ; García-Gorostiaga, I. ; Berciano, J. ; Combarros, O.</creator><creatorcontrib>Mateo, I. ; Vázquez-Higuera, J. L. ; Sánchez-Juan, P. ; Rodríguez-Rodríguez, E. ; Infante, J. ; García-Gorostiaga, I. ; Berciano, J. ; Combarros, O.</creatorcontrib><description>Objective – Glycogen synthase kinase‐3β (GSK‐3β) and cyclin‐dependent kinase 5 (CDK5) have been implicated as two major protein kinases involved in the abnormal hyperphosphorylation of tau in Alzheimer’s disease (AD) brain, and the development of neurofibrillary tangles. CDK5 regulatory subunit 1 (CDK5R1) encodes for p35, a protein required for activation of CDK5. As both CDK5R1 and GSK‐3β genes are related to phosphorylation of tau, we examined the combined contribution of these genes to the susceptibility for AD.
Methods – In a case–control study in 283 AD patients and 263 healthy controls, we examined the combined effects between CDK5R1 (3′‐UTR, rs735555) and GSK‐3β (−50, rs334558) polymorphisms on susceptibility to AD.
Results – Subjects carrying both the CDK5R1 (3′‐UTR, rs735555) AA genotype and the GSK‐3β (−50, rs334558) CC genotype had a 12.5‐fold decrease in AD risk (adjusted by age, sex and APOE status OR = 0.08, 95% CI = 0.01–0.76, P = 0.03), suggesting synergistic effects (epistasis) between both genes.
Conclusion – These data support a role for tau phosphorylation regulating genes in risk for AD.</description><identifier>ISSN: 0001-6314</identifier><identifier>EISSN: 1600-0404</identifier><identifier>DOI: 10.1111/j.1600-0404.2008.01128.x</identifier><identifier>PMID: 19154537</identifier><identifier>CODEN: ANRSAS</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Aged ; Aged, 80 and over ; Alzheimer Disease - etiology ; Alzheimer Disease - genetics ; Alzheimer's disease ; Biological and medical sciences ; Case-Control Studies ; Cyclin-Dependent Kinase 5 - genetics ; cyclin-dependent kinase 5 regulatory subunit 1 ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; epistasis ; Epistasis, Genetic ; Female ; gene polymorphism ; Glycogen Synthase Kinase 3 - genetics ; Glycogen Synthase Kinase 3 beta ; glycogen synthase kinase-3β ; Humans ; Male ; Medical sciences ; Middle Aged ; Neurology ; Phosphorylation - genetics ; Protein Subunits - genetics ; Risk Factors ; tau Proteins - genetics</subject><ispartof>Acta neurologica Scandinavica, 2009-08, Vol.120 (2), p.130-133</ispartof><rights>Copyright © 2008 The Authors. Journal compilation © 2008 Blackwell Munksgaard</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5168-f4860a09c833d19ab17f3c9bf6aa161633aad488066dfcea8ff321435a6686dd3</citedby><cites>FETCH-LOGICAL-c5168-f4860a09c833d19ab17f3c9bf6aa161633aad488066dfcea8ff321435a6686dd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1600-0404.2008.01128.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1600-0404.2008.01128.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,778,782,1414,27907,27908,45557,45558</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21691881$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19154537$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mateo, I.</creatorcontrib><creatorcontrib>Vázquez-Higuera, J. L.</creatorcontrib><creatorcontrib>Sánchez-Juan, P.</creatorcontrib><creatorcontrib>Rodríguez-Rodríguez, E.</creatorcontrib><creatorcontrib>Infante, J.</creatorcontrib><creatorcontrib>García-Gorostiaga, I.</creatorcontrib><creatorcontrib>Berciano, J.</creatorcontrib><creatorcontrib>Combarros, O.</creatorcontrib><title>Epistasis between tau phosphorylation regulating genes (CDK5R1 and GSK-3β) and Alzheimer's disease risk</title><title>Acta neurologica Scandinavica</title><addtitle>Acta Neurol Scand</addtitle><description>Objective – Glycogen synthase kinase‐3β (GSK‐3β) and cyclin‐dependent kinase 5 (CDK5) have been implicated as two major protein kinases involved in the abnormal hyperphosphorylation of tau in Alzheimer’s disease (AD) brain, and the development of neurofibrillary tangles. CDK5 regulatory subunit 1 (CDK5R1) encodes for p35, a protein required for activation of CDK5. As both CDK5R1 and GSK‐3β genes are related to phosphorylation of tau, we examined the combined contribution of these genes to the susceptibility for AD.
Methods – In a case–control study in 283 AD patients and 263 healthy controls, we examined the combined effects between CDK5R1 (3′‐UTR, rs735555) and GSK‐3β (−50, rs334558) polymorphisms on susceptibility to AD.
Results – Subjects carrying both the CDK5R1 (3′‐UTR, rs735555) AA genotype and the GSK‐3β (−50, rs334558) CC genotype had a 12.5‐fold decrease in AD risk (adjusted by age, sex and APOE status OR = 0.08, 95% CI = 0.01–0.76, P = 0.03), suggesting synergistic effects (epistasis) between both genes.
Conclusion – These data support a role for tau phosphorylation regulating genes in risk for AD.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alzheimer Disease - etiology</subject><subject>Alzheimer Disease - genetics</subject><subject>Alzheimer's disease</subject><subject>Biological and medical sciences</subject><subject>Case-Control Studies</subject><subject>Cyclin-Dependent Kinase 5 - genetics</subject><subject>cyclin-dependent kinase 5 regulatory subunit 1</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>epistasis</subject><subject>Epistasis, Genetic</subject><subject>Female</subject><subject>gene polymorphism</subject><subject>Glycogen Synthase Kinase 3 - genetics</subject><subject>Glycogen Synthase Kinase 3 beta</subject><subject>glycogen synthase kinase-3β</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neurology</subject><subject>Phosphorylation - genetics</subject><subject>Protein Subunits - genetics</subject><subject>Risk Factors</subject><subject>tau Proteins - genetics</subject><issn>0001-6314</issn><issn>1600-0404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc2O0zAUhS0EYsrAKyBv-Fsk2LHjOAsWVSgFzWiQ-BuJjXWb3LTupEmxE03LY_EgPBPOtCpLsGT5Xvk79tU5hFDOYh7W63XMFWMRk0zGCWM6ZpwnOt7dI5PTxX0yYYzxSAkuz8gj79ehSzIpH5IznvNUpiKbkNVsa30P3nq6wP4WsaU9DHS76nzYbt9Ab7uWOlwOY9ku6RJb9PRl8fYi_cQptBWdf76IxO9fr-6aafNzhXaD7oWnlfUIHqmz_uYxeVBD4_HJ8TwnX9_NvhTvo8uP8w_F9DIqU650VEutGLC81EJUPIcFz2pR5otaAXDFlRAAldSaKVXVJYKua5FwKVJQSquqEufk-eHdret-DOh7s7G-xKaBFrvBG5WlLNcq_yeYsCQJE8kA6gNYus57h7XZOrsBtzecmTEOszaj62Z03YxxmLs4zC5Inx7_GBYbrP4Kj_4H4NkRAF9CUztoS-tPXBgg51rzwL05cLe2wf1_D2CmV7OxCvrooA9h4-6kB3cTDBFZaq6v5iZn35PrIivMN_EHTte0LQ</recordid><startdate>200908</startdate><enddate>200908</enddate><creator>Mateo, I.</creator><creator>Vázquez-Higuera, J. L.</creator><creator>Sánchez-Juan, P.</creator><creator>Rodríguez-Rodríguez, E.</creator><creator>Infante, J.</creator><creator>García-Gorostiaga, I.</creator><creator>Berciano, J.</creator><creator>Combarros, O.</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><scope>BSCLL</scope><scope>IQODW</scope><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>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200908</creationdate><title>Epistasis between tau phosphorylation regulating genes (CDK5R1 and GSK-3β) and Alzheimer's disease risk</title><author>Mateo, I. ; Vázquez-Higuera, J. L. ; Sánchez-Juan, P. ; Rodríguez-Rodríguez, E. ; Infante, J. ; García-Gorostiaga, I. ; Berciano, J. ; Combarros, O.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5168-f4860a09c833d19ab17f3c9bf6aa161633aad488066dfcea8ff321435a6686dd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alzheimer Disease - etiology</topic><topic>Alzheimer Disease - genetics</topic><topic>Alzheimer's disease</topic><topic>Biological and medical sciences</topic><topic>Case-Control Studies</topic><topic>Cyclin-Dependent Kinase 5 - genetics</topic><topic>cyclin-dependent kinase 5 regulatory subunit 1</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>epistasis</topic><topic>Epistasis, Genetic</topic><topic>Female</topic><topic>gene polymorphism</topic><topic>Glycogen Synthase Kinase 3 - genetics</topic><topic>Glycogen Synthase Kinase 3 beta</topic><topic>glycogen synthase kinase-3β</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neurology</topic><topic>Phosphorylation - genetics</topic><topic>Protein Subunits - genetics</topic><topic>Risk Factors</topic><topic>tau Proteins - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mateo, I.</creatorcontrib><creatorcontrib>Vázquez-Higuera, J. L.</creatorcontrib><creatorcontrib>Sánchez-Juan, P.</creatorcontrib><creatorcontrib>Rodríguez-Rodríguez, E.</creatorcontrib><creatorcontrib>Infante, J.</creatorcontrib><creatorcontrib>García-Gorostiaga, I.</creatorcontrib><creatorcontrib>Berciano, J.</creatorcontrib><creatorcontrib>Combarros, O.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Acta neurologica Scandinavica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mateo, I.</au><au>Vázquez-Higuera, J. L.</au><au>Sánchez-Juan, P.</au><au>Rodríguez-Rodríguez, E.</au><au>Infante, J.</au><au>García-Gorostiaga, I.</au><au>Berciano, J.</au><au>Combarros, O.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epistasis between tau phosphorylation regulating genes (CDK5R1 and GSK-3β) and Alzheimer's disease risk</atitle><jtitle>Acta neurologica Scandinavica</jtitle><addtitle>Acta Neurol Scand</addtitle><date>2009-08</date><risdate>2009</risdate><volume>120</volume><issue>2</issue><spage>130</spage><epage>133</epage><pages>130-133</pages><issn>0001-6314</issn><eissn>1600-0404</eissn><coden>ANRSAS</coden><abstract>Objective – Glycogen synthase kinase‐3β (GSK‐3β) and cyclin‐dependent kinase 5 (CDK5) have been implicated as two major protein kinases involved in the abnormal hyperphosphorylation of tau in Alzheimer’s disease (AD) brain, and the development of neurofibrillary tangles. CDK5 regulatory subunit 1 (CDK5R1) encodes for p35, a protein required for activation of CDK5. As both CDK5R1 and GSK‐3β genes are related to phosphorylation of tau, we examined the combined contribution of these genes to the susceptibility for AD.
Methods – In a case–control study in 283 AD patients and 263 healthy controls, we examined the combined effects between CDK5R1 (3′‐UTR, rs735555) and GSK‐3β (−50, rs334558) polymorphisms on susceptibility to AD.
Results – Subjects carrying both the CDK5R1 (3′‐UTR, rs735555) AA genotype and the GSK‐3β (−50, rs334558) CC genotype had a 12.5‐fold decrease in AD risk (adjusted by age, sex and APOE status OR = 0.08, 95% CI = 0.01–0.76, P = 0.03), suggesting synergistic effects (epistasis) between both genes.
Conclusion – These data support a role for tau phosphorylation regulating genes in risk for AD.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>19154537</pmid><doi>10.1111/j.1600-0404.2008.01128.x</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0001-6314 |
| ispartof | Acta neurologica Scandinavica, 2009-08, Vol.120 (2), p.130-133 |
| issn | 0001-6314 1600-0404 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_67509869 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Aged Aged, 80 and over Alzheimer Disease - etiology Alzheimer Disease - genetics Alzheimer's disease Biological and medical sciences Case-Control Studies Cyclin-Dependent Kinase 5 - genetics cyclin-dependent kinase 5 regulatory subunit 1 Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases epistasis Epistasis, Genetic Female gene polymorphism Glycogen Synthase Kinase 3 - genetics Glycogen Synthase Kinase 3 beta glycogen synthase kinase-3β Humans Male Medical sciences Middle Aged Neurology Phosphorylation - genetics Protein Subunits - genetics Risk Factors tau Proteins - genetics |
| title | Epistasis between tau phosphorylation regulating genes (CDK5R1 and GSK-3β) and Alzheimer's disease risk |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-16T11%3A39%3A20IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Epistasis%20between%20tau%20phosphorylation%20regulating%20genes%20(CDK5R1%20and%20GSK-3%CE%B2)%20and%20Alzheimer's%20disease%20risk&rft.jtitle=Acta%20neurologica%20Scandinavica&rft.au=Mateo,%20I.&rft.date=2009-08&rft.volume=120&rft.issue=2&rft.spage=130&rft.epage=133&rft.pages=130-133&rft.issn=0001-6314&rft.eissn=1600-0404&rft.coden=ANRSAS&rft_id=info:doi/10.1111/j.1600-0404.2008.01128.x&rft_dat=%3Cproquest_cross%3E20221684%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=20221684&rft_id=info:pmid/19154537&rfr_iscdi=true |