Abeta peptide immunization restores blood-brain barrier integrity in Alzheimer disease

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Dara L DicksteinWilfred A Jefferies

Abstract

Immunization with amyloid beta (Abeta) peptides or passive immunization with antibodies against Abeta has been reported to reduce plaque burden, neuritic dystrophy, early Tau pathology, microgliosis as well as reversing learning and memory deficits. This has created a central paradox: how does vaccination in peripheral tissues reduce plaque burden in the brain? No single explanation for these phenomena has yet been presented. To reconcile these observations, we demonstrate that the integrity of the blood-brain barrier (BBB), a structural barrier between the brain and the blood, is compromised in Tg2576 Alzheimer disease (AD) model mice. We immunized Tg2576 mice with Abeta before and after the onset of AD-type neuropathology and observed that BBB permeability, amyloid burden, and microgliosis are decreased in immunized mice. It is concluded that the integrity of the BBB is disrupted in AD mice, and after Abeta immunization the immune system clears Abeta from sources in the brain as it would in peripheral organs lacking barriers. Once Abeta is removed, the integrity of the BBB is restored. The data therefore provide an intellectual framework for understanding how the immune system can clear amyloid deposits from AD brains and sug...Continue Reading

References

Apr 1, 1988·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·O UyamaM Sugita
Oct 1, 1981·European Journal of Immunology·J M Austyn, S Gordon
Oct 31, 1998·Brain Research. Molecular Brain Research·R N KalariaW D Lust
Apr 30, 1999·Progress in Neurobiology·W J StreitN A Pennell
Jun 20, 2000·Neurobiology of Aging·H AkiyamaT Wyss-Coray
Nov 18, 2000·American Journal of Physiology. Cell Physiology·R GiriV K Kalra
Jul 5, 2001·Proceedings of the National Academy of Sciences of the United States of America·R B DeMattosD M Holtzman
Aug 8, 2001·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·J XuC Y Hsu
Jan 5, 2002·Neurobiology of Aging·P Grammas, R Ovase
Jan 30, 2003·Annals of Medicine·Peter T NelsonEhud Lavi
Feb 25, 2003·Lancet·Anthony H Vagnucci, William W Li
Mar 8, 2003·Stroke; a Journal of Cerebral Circulation·J M WardlawJ Starr
May 10, 2003·Neurochemical Research·Cynthia A LemereTimothy J Seabrook
Jan 28, 2004·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Maki UjiieWilfred A Jefferies
Apr 6, 2004·Biochemical and Biophysical Research Communications·Tatsuya KondoC Ronald Kahn
Jun 15, 2004·Neuroreport·Aileen I Pogue, Walter J Lukiw
Jun 24, 2004·Neurobiology of Aging·Shyamala MruthintiRosann F Schade
Jul 3, 2004·The Journal of Clinical Investigation·Dennis W Dickson
Jul 20, 2004·Histochemistry and Cell Biology·Masaki UenoToshitaka Nakagawa

❮ Previous
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Citations

Feb 19, 2011·Annals of Biomedical Engineering·Alexander J LinBruce J Tromberg
Jul 5, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Aaron C HirkoJeffery A Hughes
Aug 1, 2007·The Journal of Experimental Medicine·Justin PaulJerry P Melchor
Sep 23, 2011·Journal of Neuroinflammation·Qing-Hong ZhangYong-Ming Yao
May 1, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Huaqi XiongWandong Zhang
May 27, 2009·International Journal of Molecular Sciences·Samir Kumar-Singh
Feb 1, 2008·Aging Health·Gene L Bowman, Joseph F Quinn
Feb 1, 2007·Proceedings of the National Academy of Sciences of the United States of America·William V NikolicJun Tan
Apr 25, 2014·Cellular and Molecular Life Sciences : CMLS·Mario VallonCalvin J Kuo
Jun 23, 2012·Cellular and Molecular Life Sciences : CMLS·Yasmina MansoJuan Hidalgo
Apr 2, 2008·Journal of Neuropathology and Experimental Neurology·John E Donahue, Conrad E Johanson
Dec 29, 2011·Advanced Drug Delivery Reviews·William A Banks
Jun 12, 2014·Journal of Neuropathology and Experimental Neurology·Nina SchultzMalin Wennström
Mar 1, 2013·Scientific Reports·Kaan E BironWilfred A Jefferies
Jul 15, 2015·Histochemistry and Cell Biology·Amanda J BrockH Anne Pereira
Nov 19, 2014·Frontiers in Cellular Neuroscience·Anna Carolina Carvalho da FonsecaFlavia Regina Souza Lima
Mar 7, 2009·Journal of the Neurological Sciences·Bogdan O PopescuNenad Bogdanovic
Jun 27, 2017·Biosensors & Bioelectronics·K RajasekharThimmaiah Govindaraju
Nov 28, 2009·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Ryszard PlutaMirosław Jabłoński
Jan 27, 2010·The Mount Sinai Journal of Medicine, New York·Dara L DicksteinPatrick R Hof
Dec 17, 2008·The Journal of Biological Chemistry·Said AbdAllaUrsula Quitterer
Jun 17, 2011·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Yasmina MansoJuan Hidalgo
Jun 3, 2015·Biology of the Cell·Kinga G BlecharzPeter Vajkoczy
Apr 29, 2009·The Journal of Comparative Neurology·Howard J Federoff
May 16, 2014·Reviews in the Neurosciences·Zareen Amtul, Jeffrey D Hepburn

❮ Previous
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