Alex Bishop will be presenting the paper on Friday (3/4/2011) at 4:00 PM in Roskamp Institute.
Title: Identification of Candidate IgG Biomarkers for Alzheimer’s Disease via Combinatorial Library Screening
Cell 144, 132–142, January 7, 2011
Journal Club is held every Friday. For change in schedule please check our Twitter account or Facebook page.
The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949
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Dr Fiona Crawford is presenting the Roskamp Institute Gulf War Illness Research Program
to the Research Advisory Committee on Gulf War Veterans’ Illnesses in Washington, DC
today. Although there has been surprisingly little media coverage, it is the 20th anniversary of the 1991 conflict. Dr
Crawford together with other experts and veterans suffering from Gulf War Illness are discussing what is now known about this chronic
multi-symptom illness, and how basic and clinical research programs such as the one at Roskamp are advancing toward effective treatment for this devastating
disease.
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February 14, 2011
Dr. Bachmeier and Dr. Paris recently published an article in Microcirculation titled “Epitope-dependent effects of beta-amyloid antibodies on beta-amyloid clearance in an in vitro model of the blood-brain barrier”. This report offers an explanation as to why some antibody-based immunotherapies are more effective than others in lowering brain amyloid levels in AD.
Abstract
Objective: To investigate the role of the receptor for advanced glycation end products (RAGE) in the epitope-dependent effects of beta-amyloid (Aβ) antibodies used as a peripheral sink therapy in Alzheimer’s disease.
Methods: An in vitro model of the blood-brain barrier (BBB) was used to examine the effect of various Aβ antibodies or Aβ peptide fragments on Aβ exchange across the BBB.
Results: An N-terminal Aβ antibody significantly enhanced the basolateral-to-apical transcytosis of fluorescein-Aβ(1-42) across the BBB model (41%), while no effect was apparent with a C-terminal Aβ antibody. Interestingly, modulation of RAGE in the presence of a C-terminal Aβ antibody resulted in a 65% increase in Aβ clearance of across the BBB model, suggesting the C-terminal antibody-Aβ complex is susceptible to RAGE transport. Additionally, N-terminal peptide fragments of Aβ attenuated the brain penetration of full length Aβ in the BBB model, indicating the N-terminal region of Aβ is required for brain uptake.
Conclusions: Antibodies masking the N-terminal region of Aβ increase Aβ clearance across the BBB by preventing Aβ from interacting with the RAGE transporter, whereas antibodies bound to the C-terminus of Aβ are taken up by RAGE and, hence, do not influence the BBB clearance of Aβ.
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Benoit Mouzon will be presenting the paper on Friday (2/25/2011) at 4:00 PM in Roskamp Institute.
Title: Tau-Induced Defects in Synaptic Plasticity, Learning, and Memory Are Reversible in Transgenic Mice after Switching
Off the Toxic Tau Mutant.
The Journal of Neuroscience, February 16, 2011 • 31(7):2511–2525 • 2511
Journal Club is held every Friday. For change in schedule please check our Twitter account or Facebook page.
The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949
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1-13-2011
Dr. Corbin Bachmeier of the Roskamp Institute in collaboration with Dr. Gary Levin of the University of Southern Nevada recently received a grant from Pfizer to study the effect of two antidepressant medications currently on the market, venlafaxine (Effexor) and desvenlafaxine (Pristiq), on the expression of the drug efflux transport proteins P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) in vivo. This work is a continuation of their previous efforts, supported through a grant from Wyeth Pharmaceuticals, which determined that venlafaxine induces drug efflux protein expression in brain endothelial cells, an in vitro model of the blood-brain barrier (BBB), in a dose dependant manner. Moreover, these effects were functionally significant as treatment with venlafaxine reduced the permeability of a known drug efflux probe, rhodamine 123, across the BBB model and Caco-2 cell monolayers, a model of intestinal absorption. Conversely, treatment with desvenlafaxine in the BBB model did not result in a statistically significant change in the expression of either P-gp or BCRP nor did desvenlafaxine impact the permeability of R123 across the BBB model or Caco-2 monolayers. As it is difficult to predict clinical outcomes based solely on in vitro observations, the current in vivo studies will examine the impact of these compounds on drug efflux protein expression in a live animal. In doing so, these studies will provide a better understanding of the potential for drug-drug interactions and the relevance of these effects to a clinical setting.
The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949
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Scott Ferguson will be presenting the paper on Friday (2/11/2011) at 4:00 PM in Roskamp Institute.
Title: Neurogenesis in Adult Human Brain after Traumatic Brain Injury.
J Neurotrauma. 2011 Jan 30. [Epub ahead of print]
Journal Club is held every Friday. For change in schedule please check our Twitter account or Facebook page.
The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949
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Ekta Shah will be presenting the paper on Friday (2/4/2011) at 4:00 PM in Roskamp Institute.
Title: Apolipoprotein E4 domain interaction mediates detrimental effects on mitochondria and is a potential therapeutic target for Alzheimer’s disease.
J Biol Chem. 2010 Nov 30. [Epub ahead of print]
Journal Club is held every Friday. For change in schedule please check our Twitter account or Facebook page.
The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949
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