ApoE-Directed Therapeutics Rapidly Clear ß-Amyloid and Reverse Deficits in AD Mouse Models
Alzheimer's disease (AD) is associated with impaired clearance of ß-amyloid (Aß) from the brain, a process normally facilitated by apolipoprotein E (apoE). ApoE expression is transcriptionally induced through the action of the nuclear receptors peroxisome proliferator-activated receptor gamma a...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2012-03, Vol.335 (6075), p.1503-1506 |
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| creator | Cramer, Paige E. Cirrito, John R. Wesson, Daniel W. Lee, C. Y. Daniel Karlo, J. Colleen Zinn, Adriana E. Casali, Brad T. Restivo, Jessica L. Goebel, Whitney D. James, Michael J. Brunden, Kurt R. Wilson, Donald A. Landreth, Gary E. |
| description | Alzheimer's disease (AD) is associated with impaired clearance of ß-amyloid (Aß) from the brain, a process normally facilitated by apolipoprotein E (apoE). ApoE expression is transcriptionally induced through the action of the nuclear receptors peroxisome proliferator-activated receptor gamma and liver X receptors in coordination with retinoid X receptors (RXRs). Oral administration of the RXR agonist bexarotene to a mouse model of AD resulted in enhanced clearance of soluble Aß within hours in an apoE-dependent manner. Aß plaque area was reduced more than 50% within just 72 hours. Furthermore, bexarotene stimulated the rapid reversal of cognitive, social, and olfactory deficits and improved neural circuit function. Thus, RXR activation stimulates physiological Aß clearance mechanisms, resulting in the rapid reversal of a broad range of Aß-induced deficits. |
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Colleen ; Zinn, Adriana E. ; Casali, Brad T. ; Restivo, Jessica L. ; Goebel, Whitney D. ; James, Michael J. ; Brunden, Kurt R. ; Wilson, Donald A. ; Landreth, Gary E.</creator><creatorcontrib>Cramer, Paige E. ; Cirrito, John R. ; Wesson, Daniel W. ; Lee, C. Y. Daniel ; Karlo, J. Colleen ; Zinn, Adriana E. ; Casali, Brad T. ; Restivo, Jessica L. ; Goebel, Whitney D. ; James, Michael J. ; Brunden, Kurt R. ; Wilson, Donald A. ; Landreth, Gary E.</creatorcontrib><description>Alzheimer's disease (AD) is associated with impaired clearance of ß-amyloid (Aß) from the brain, a process normally facilitated by apolipoprotein E (apoE). ApoE expression is transcriptionally induced through the action of the nuclear receptors peroxisome proliferator-activated receptor gamma and liver X receptors in coordination with retinoid X receptors (RXRs). Oral administration of the RXR agonist bexarotene to a mouse model of AD resulted in enhanced clearance of soluble Aß within hours in an apoE-dependent manner. Aß plaque area was reduced more than 50% within just 72 hours. Furthermore, bexarotene stimulated the rapid reversal of cognitive, social, and olfactory deficits and improved neural circuit function. Thus, RXR activation stimulates physiological Aß clearance mechanisms, resulting in the rapid reversal of a broad range of Aß-induced deficits.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><language>eng</language><publisher>American Association for the Advancement of Science</publisher><subject>Alzheimers disease ; Behavioral neuroscience ; Hippocampus ; Mice ; Microglia ; Neural conduction ; Odors ; Receptors ; T tests ; Vehicles</subject><ispartof>Science (American Association for the Advancement of Science), 2012-03, Vol.335 (6075), p.1503-1506</ispartof><rights>Copyright © 2012 American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/41507542$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/41507542$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,780,784,803,58017,58250</link.rule.ids></links><search><creatorcontrib>Cramer, Paige E.</creatorcontrib><creatorcontrib>Cirrito, John R.</creatorcontrib><creatorcontrib>Wesson, Daniel W.</creatorcontrib><creatorcontrib>Lee, C. 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ApoE expression is transcriptionally induced through the action of the nuclear receptors peroxisome proliferator-activated receptor gamma and liver X receptors in coordination with retinoid X receptors (RXRs). Oral administration of the RXR agonist bexarotene to a mouse model of AD resulted in enhanced clearance of soluble Aß within hours in an apoE-dependent manner. Aß plaque area was reduced more than 50% within just 72 hours. Furthermore, bexarotene stimulated the rapid reversal of cognitive, social, and olfactory deficits and improved neural circuit function. Thus, RXR activation stimulates physiological Aß clearance mechanisms, resulting in the rapid reversal of a broad range of Aß-induced deficits.</description><subject>Alzheimers disease</subject><subject>Behavioral neuroscience</subject><subject>Hippocampus</subject><subject>Mice</subject><subject>Microglia</subject><subject>Neural conduction</subject><subject>Odors</subject><subject>Receptors</subject><subject>T tests</subject><subject>Vehicles</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid/><recordid>eNqFjj0KgzAYQENpofbnCIXvAoH419ZR1NLFRdw6SDCfNBKNJFrwND1ML1aH7p0evLe8FXFcFoU08pi_Jg5j_ple2SXckp21LWNLi3yHPOJBZzSVBusRBZRPNHzAaZS1hYIPUqgZEoXcwOdN425WWgrgvYACX2gsQoqNrOVoQfYQp5DraZG5FqjsgWwariwef9yT0y0rkztt7ahNNRjZcTNXgRsuX4Hn_-tfBVk_Pg</recordid><startdate>20120323</startdate><enddate>20120323</enddate><creator>Cramer, Paige E.</creator><creator>Cirrito, John R.</creator><creator>Wesson, Daniel W.</creator><creator>Lee, C. 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Colleen</creatorcontrib><creatorcontrib>Zinn, Adriana E.</creatorcontrib><creatorcontrib>Casali, Brad T.</creatorcontrib><creatorcontrib>Restivo, Jessica L.</creatorcontrib><creatorcontrib>Goebel, Whitney D.</creatorcontrib><creatorcontrib>James, Michael J.</creatorcontrib><creatorcontrib>Brunden, Kurt R.</creatorcontrib><creatorcontrib>Wilson, Donald A.</creatorcontrib><creatorcontrib>Landreth, Gary E.</creatorcontrib><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cramer, Paige E.</au><au>Cirrito, John R.</au><au>Wesson, Daniel W.</au><au>Lee, C. Y. Daniel</au><au>Karlo, J. Colleen</au><au>Zinn, Adriana E.</au><au>Casali, Brad T.</au><au>Restivo, Jessica L.</au><au>Goebel, Whitney D.</au><au>James, Michael J.</au><au>Brunden, Kurt R.</au><au>Wilson, Donald A.</au><au>Landreth, Gary E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ApoE-Directed Therapeutics Rapidly Clear ß-Amyloid and Reverse Deficits in AD Mouse Models</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><date>2012-03-23</date><risdate>2012</risdate><volume>335</volume><issue>6075</issue><spage>1503</spage><epage>1506</epage><pages>1503-1506</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><abstract>Alzheimer's disease (AD) is associated with impaired clearance of ß-amyloid (Aß) from the brain, a process normally facilitated by apolipoprotein E (apoE). ApoE expression is transcriptionally induced through the action of the nuclear receptors peroxisome proliferator-activated receptor gamma and liver X receptors in coordination with retinoid X receptors (RXRs). Oral administration of the RXR agonist bexarotene to a mouse model of AD resulted in enhanced clearance of soluble Aß within hours in an apoE-dependent manner. Aß plaque area was reduced more than 50% within just 72 hours. Furthermore, bexarotene stimulated the rapid reversal of cognitive, social, and olfactory deficits and improved neural circuit function. Thus, RXR activation stimulates physiological Aß clearance mechanisms, resulting in the rapid reversal of a broad range of Aß-induced deficits.</abstract><pub>American Association for the Advancement of Science</pub></addata></record> |
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| subjects | Alzheimers disease Behavioral neuroscience Hippocampus Mice Microglia Neural conduction Odors Receptors T tests Vehicles |
| title | ApoE-Directed Therapeutics Rapidly Clear ß-Amyloid and Reverse Deficits in AD Mouse Models |
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