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Sagare A, Deane R, Bell RD, Johnson B, Hamm K, Pendu R, Marky A, Lenting PJ, Wu Z, Zarcone T, Goate A, Mayo K, Perlmutter D, Coma M, Zhong Z, Zlokovic BV.
Clearance of amyloid-beta by circulating lipoprotein receptors. Nat Med.
2007 Sep;13(9):1029-31.
PubMed Abstract
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Comment by: John Trojanowski, ARF Advisor
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Submitted 24 August 2007
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Posted 27 August 2007
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I recommend this paper
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Comment by: Cynthia Lemere, ARF Advisor (Disclosure)
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Submitted 26 August 2007
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Posted 27 August 2007
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I recommend this paper
Sagare et al. report for the first time, the ability of systemically administered Aß-binding, recombinant soluble LRP cluster IV (sLRP-IV) to lower cerebral Aß levels and increase peripheral Aß in plasma. This provides proof-of-concept that sLRP-IV may have therapeutic potential for the prevention and, possibly, the treatment of AD.
The authors suggest that sLRP-IV has potential as a systemic Aß-lowering therapy by virtue of its ability to enhance cerebral blow flow, enhance efflux of Aß from brain to blood, and prevent re-uptake of Aß from blood to brain. As a result, and based on their APP tg mouse studies, they predict that such a treatment will prevent or reduce Aß deposition in brain, thereby staving off plaque-associated changes such as gliosis and neuritic dystrophy and preventing learning and memory deficits.
View all comments by Cynthia Lemere
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Comment by: Randall Bateman
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Submitted 28 August 2007
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Posted 28 August 2007
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I recommend this paper
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REAGENTS/MATERIAL:
Antibodies used in this study are: goat anti-mouse-ApoE (M20) (Santa Cruz); goat biotinylated anti-human-ApoE (Biodesign); rabbit anti-human-Aβ40 (Invitrogen); rabbit anti-human-Aβ42 (Invitrogen); rabbit biotinilated anti-mouse/human-tPA (Innovative Research); LRP-IV (MW ~ 55 kDa) was detected with an LRP-IV specific antiserum (Croy et al., Biochemistry, 42, 13049, 2003); goat anti-sLRP (N-20) (Santa Cruz); mouse monoclonal anti-mouse-Aβ40 for ELISA, (Invitrogen); rabbit biotinilated anti-Aβ40 for ELISA, (Invitrogen); rabbit biotinilated anti-Aβ42 for ELISA, (Invitrogen); mouse monoclonal anti-RAP (MA7F1) (Oxford Biomedical); rat monoclonal anti-mouse-Apo J (327020) (R&D Systems) Human specific ELISA kits anti-human-Aβ40 ELISA, (KHB3481, Invitrogen) and anti-human-Aβ42 ELISA, (KHB3441, Invitrogen); rat monoclonal anti-mouse-CD31 (BD Pharmingen); mouse monoclonal anti-LRP, light chain (5A6) (Calbiochem, EMD Chemicals); mouse monoclonal anti-LDLR (15C8) (Calbiochem, EMD Chemicals); kit anti-mouse-tPA, ELISA, (Molecular Innovations); kit anti-mouse-pro-MMP-9, ELISA, (R&D Systems); mouse monoclonal anti-LRP, heavy chain, N-terminus (8G1) (Calbiochem, EMD Chemicals); mouse monoclonal anti-human-APO J (G7) (Quidel Corp)
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