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Abstract
Background: While apolipoprotein E4 (apoE4) is highly correlated with the development of Alzheimer’s disease (AD), its role in AD pathology and, in particular, beta-amyloid (Aβ) removal from the brain, is not clearly defined. Objective: To elucidate the influence of apoE on the clearance of Aβ across the BBB. Methods: Aβ(1-42) was intracerebrally administered to transgenic mice expressing human apoE isoforms and examined in the periphery. Results: ApoE3 and apoE4 mice had 5-times and 2-times, respectively, more Aβ(1-42) appearing in the plasma than wild-type or apoE knockout mice, indicating an enhanced clearance of Aβ from the brain to the periphery. In vitro, unbound basolateral apoE3 (i.e., not bound to Aβ), and to a lesser extent unbound apoE4, at concentrations ≤10nM facilitated basolateral-to-apical fluorescein-Aβ(1-42) transcytosis across a blood-brain barrier (BBB) model, while apoE isoforms bound to Aβ significantly disrupted Aβ transcytosis. Additionally, following apical exposure to the BBB model, we found apoE4 bound to Aβ is able to penetrate the BBB more readily than apoE3 bound to Aβ and does so via the RAGE transporter. Conclusion: These studies indicate a multifaceted, isoform-dependent role for apoE in the exchange of Aβ across the BBB and may partially explain the association of apoE4 and Aβ brain accumulation in AD.

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Tang-Schomer MD, Johnson VE, Baas PW, Stewart W, Smith DH. Partial interruption of axonal transport due to microtubule breakage accounts for the formation of periodic varicosities after traumatic axonal injury. Exp Neurol. 2012 Jan;233(1):364-72. Epub 2011 Nov 4. PMID: 22079153

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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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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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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SARASOTA, FL – As the National Football League takes steps to reduce concussions and other traumatic brain injuries (TBIs), a new film being premiered at the Sarasota Film Festival tells the tragic personal story of NFL star Kevin Turner.  After an eight-year career with the New England Patriots and Philadelphia Eagles, Kevin Turner now suffers from amyotrophic lateral sclerosis (ALS), a fatal nervous system condition also known as Lou Gehrig’s disease.

“Kevin is a gentle but broken man of 42, a football superstar forced to reflect on the price he is paying for his glory years,” said filmmaker Jon Frankel in advance of the April 19 world premier of his movie “American Man” at the Opera House. “In the decade since he retired, Kevin lost his job, his money, his marriage and even, he thinks, his mind.”
Following the April 19 premiere, Dr. Fiona Crawford, associate director of The Roskamp Institute, will join Turner and Frankel for a panel discussion of the latest research into the long-term impact of multiple head injuries.  “We have been modeling repetitive head injury in our Sarasota laboratory, and found there is a significant difference in terms of behavior and pathology compared with a single injury,” said Crawford, whose findings were presented at a recent meeting of the International Brain Injury Association in Scotland. “There are cognitive deficits with the repetitive injury, but no obvious deficits after 12 months with a single injury,” said Crawford.

Frankel, a correspondent for HBO-REAL Sports, shot the film about Turner’s life from August 2010 to fall 2011.  “He has lost considerable use of his hands and arms but still drives,” he said. “The disease has not hit his legs yet. He is beginning to have a little more trouble talking.  But he still sounds pretty darn good since being diagnosed two years ago.”

Turner was drafted by the Patriots as a fullback in 1992, joined Philadelphia three years later and ended his playing career in 1999. He believes the multiple concussions and head injuries from football led to the onset of ALS.  Turner is believed to be the 14th former NFL player diagnosed with ALS since 1960, a rate twice as likely than someone not suffering from repeated concussions.

In recent years, the NFL has tightened its rules regarding helmet-to-helmet “hits” and how quickly a player can return to the game after suffering a concussion. The spring, the NFL severely disciplined the New Orleans Saints for running a bounty system that rewarded team members who injured opposing players.

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For tickets to the AMERICAN MAN film premiere:

http://sarasota.festivalgenius.com/2012/films/americanman_jonfrankel_sarasota2012

Date: Thursday, April 19, 2012

Where:  Sarasota Opera House

Time: VIP Reception to Benefit The Roskamp Institute begins 6pm

Screening at 7:30pm, Panel discussion immediately follows

The Roskamp Institute is a scientific research facility devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders.  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.

The Institute is located in Sarasota, Florida where it operates a memory clinic.

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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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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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Journal Club is held every Friday. For change in schedule please check our Twitter account or Facebook page.

Kimchi Nguyen, Charlotte D’Mello, Tai Le, Stefan Urbanski, Mark G. Swain, Regulatory T cells suppress sickness behaviour development without altering liver injury in cholestatic mice, Journal of Hepatology, Volume 56, Issue 3, March 2012, Pages 626-631, ISSN 0168-8278, 10.1016/j.jhep.2011.09.014.

(http://www.sciencedirect.com/science/article/pii/S0168827811007768)

Rita Garcia-Martinez, Juan Cordoba, Liver-induced inflammation hurts the brain, Journal of Hepatology, Volume 56, Issue 3, March 2012, Pages 515-517, ISSN 0168-8278, 10.1016/j.jhep.2011.11.003.

(http://www.sciencedirect.com/science/article/pii/S0168827811008026)

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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Condello C.,  Schain A., Grutzendler J. Multicolor time-stamp reveals the dynamics and toxicity of amyloid deposition. 2011. Scientific Reports 1, Article number: 19 doi:10.1038/srep00019

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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