PMID- 22323736
OWN - NLM
STAT- MEDLINE
DCOM- 20120409
LR  - 20220309
IS  - 1095-9203 (Electronic)
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 335
IP  - 6075
DP  - 2012 Mar 23
TI  - ApoE-directed therapeutics rapidly clear beta-amyloid and reverse deficits in AD 
      mouse models.
PG  - 1503-6
LID - 10.1126/science.1217697 [doi]
AB  - Alzheimer's disease (AD) is associated with impaired clearance of beta-amyloid (Abeta) 
      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 Abeta within hours in an apoE-dependent manner. Abeta 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 Abeta clearance mechanisms, 
      resulting in the rapid reversal of a broad range of Abeta-induced deficits.
FAU - Cramer, Paige E
AU  - Cramer PE
AD  - Department of Neurosciences, Case Western Reserve University School of Medicine, 
      Cleveland, OH 44106, USA.
FAU - Cirrito, John R
AU  - Cirrito JR
FAU - Wesson, Daniel W
AU  - Wesson DW
FAU - Lee, C Y Daniel
AU  - Lee CY
FAU - Karlo, J Colleen
AU  - Karlo JC
FAU - Zinn, Adriana E
AU  - Zinn AE
FAU - Casali, Brad T
AU  - Casali BT
FAU - Restivo, Jessica L
AU  - Restivo JL
FAU - Goebel, Whitney D
AU  - Goebel WD
FAU - James, Michael J
AU  - James MJ
FAU - Brunden, Kurt R
AU  - Brunden KR
FAU - Wilson, Donald A
AU  - Wilson DA
FAU - Landreth, Gary E
AU  - Landreth GE
LA  - eng
GR  - AG030482-03S1/AG/NIA NIH HHS/United States
GR  - P50 AG005681/AG/NIA NIH HHS/United States
GR  - R01-AG037693/AG/NIA NIH HHS/United States
GR  - R01 DC003906/DC/NIDCD NIH HHS/United States
GR  - R01 AG030482/AG/NIA NIH HHS/United States
GR  - K01 AG029524/AG/NIA NIH HHS/United States
GR  - P50-AG005681/AG/NIA NIH HHS/United States
GR  - DC003906/DC/NIDCD NIH HHS/United States
GR  - R01 AG037693/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120209
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Liver X Receptors)
RN  - 0 (Orphan Nuclear Receptors)
RN  - 0 (PPAR gamma)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Tetrahydronaphthalenes)
RN  - A61RXM4375 (Bexarotene)
SB  - IM
CIN - Science. 2012 Mar 23;335(6075):1447-8. PMID: 22442467
CIN - Nat Rev Drug Discov. 2012 Apr;11(4):271. PMID: 22460119
CIN - Science. 2013 May 24;340(6135):924-c. PMID: 23704552
CIN - Science. 2013 May 24;340(6135):924-d. PMID: 23704553
CIN - Science. 2013 May 24;340(6135):924-e. PMID: 23704554
CIN - Science. 2013 May 24;340(6135):924-f. PMID: 23704555
CIN - Science. 2013 May 24;340(6135):924-g. PMID: 23704556
MH  - Alzheimer Disease/*drug therapy/*metabolism
MH  - Amyloid beta-Peptides/*metabolism
MH  - Amyloidosis/drug therapy/metabolism
MH  - Animals
MH  - Apolipoproteins E/*metabolism
MH  - Astrocytes/drug effects/metabolism
MH  - Behavior, Animal/drug effects
MH  - Bexarotene
MH  - Brain/drug effects/*metabolism
MH  - Disease Models, Animal
MH  - Extracellular Fluid/drug effects/metabolism
MH  - Liver X Receptors
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Microglia/drug effects/metabolism
MH  - Molecular Targeted Therapy
MH  - Odorants
MH  - Olfactory Pathways/drug effects/physiology
MH  - Orphan Nuclear Receptors/metabolism
MH  - PPAR gamma/metabolism
MH  - Phagocytosis
MH  - Plaque, Amyloid/drug therapy
MH  - Retinoid X Receptors/agonists/metabolism
MH  - Tetrahydronaphthalenes/*pharmacology/*therapeutic use
PMC - PMC3651582
MID - NIHMS460482
EDAT- 2012/02/11 06:00
MHDA- 2012/04/10 06:00
PMCR- 2013/05/11
CRDT- 2012/02/11 06:00
PHST- 2012/02/11 06:00 [entrez]
PHST- 2012/02/11 06:00 [pubmed]
PHST- 2012/04/10 06:00 [medline]
PHST- 2013/05/11 00:00 [pmc-release]
AID - science.1217697 [pii]
AID - 10.1126/science.1217697 [doi]
PST - ppublish
SO  - Science. 2012 Mar 23;335(6075):1503-6. doi: 10.1126/science.1217697. Epub 2012 
      Feb 9.