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Linda Van Eldik, Ph.D.
University of Kentucky Research Foundation
Lexington, KY
Title:
Attenuating proinflammatory cytokine up-regulation as an AD therapeutic strategy
Non-Technical Title:
Testing novel CNS therapeutics for efficacy
Duration:
April 1, 2008 - March 31, 2011
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Summary: The hypothesis to be tested in this project is that orally delivered drugs that inhibit the immune response by activated glia can reduce Alzheimer's related neurodegeneration.
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Program: Alzheimer's Disease
Award Type: Standard
$400,000
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Philip Verghese, Ph.D.
Washington University, School of Medicine
Saint Louis, MO
Title:
Apolipoprotein E Isoforms and Amyloid Beta Metabolism
Non-Technical Title:
Role of Brain HDL (“good cholesterol”)-Like Particles in Amyloid Beta Metabolism
Duration:
April 1, 2010 - March 31, 2012
Mentor:
David Holtzman, M.D.
Washington University, School of Medicine
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Summary: Apolipoprotein E appears to influence Alzheimer’s disease pathogenesis in large part due to its ability to modulate amyloidbeta metabolism and structure. This ultimately influences the probability of amyloid beta aggregation. Our goal is to understand how apoE isoforms and lipid modulating molecules like ATP-binding cassette transporter A1 (ABCA1) take part in amyloid beta metabolism in the brain.
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Program: Alzheimer's Disease
Award Type: Research Fellowship
$100,000
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Ning Wang, Ph.D.
Northwestern University
Evanston, IL
Title:
Compartment And Tissue Specific Toxicity Of Amyloid Beta 1-42 In C. Elegans
Non-Technical Title:
A Story From The Humanized Worms: Comprehensive Study Of Cellular Toxicity Of Amyloid Beta 1-42
Duration:
April 1, 2009 - March 31, 2011
Mentor:
Richard Morimoto, Ph.D.
Northwestern University
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Summary: What is the cellular basis of amyloid beta toxicity in different cellular compartments and tissue types? What, if any, are the compartment and tissue specific signaling pathways and genetic networks that are involved in modulating amyloid beta toxicity? Is it possible to regulate these genetic networks to provide insight into therapeutic design?
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Program: Alzheimer's Disease
Award Type: Research Fellowship
$100,000
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Chunyu Wang, M.D., Ph.D.
Rensselaer Polytechnic Institute
Troy, NY
Title:
Structural Basis Of FAD Mutations Within The Transmembrane Domain Of APP
Non-Technical Title:
Structural Biology Of Amyloid Beta Generation
Duration:
April 1, 2009 - March 31, 2011
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Summary: This project aims to define the structural characteristics of trans-membrane portion of Amyloid Precursor Protein (APPTM ) as a gamma-secretase substrate that plays a role in determining the amyloid beta 42/amyloid beta 40 ratio. This will be achieved by combining a gamma-secretase assay and structural determination of normal and a variety of mutant forms of APPTM.
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Program: Alzheimer's Disease
Award Type: Pilot
$150,000
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David Westaway, Ph.D.
University of Alberta
Edmonton, Canada
Title:
Complex modulation in gamma-secretase interactions
Non-Technical Title:
Understanding the components in an Alzheimer's drug target
Duration:
April 1, 2010 - March 31, 2012
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Summary: The activity of the gamma-secretase protein complex provided a crucial step in limiting Alzheimer’s disease spread, but is tricky to consider as a drug target because this enzyme can be configured from different molecular modules. To understand the logic of how each of these different modules interact, we will methodically take the enzyme apart at the molecular level. Through this process, we can begin to answer which drug is best suited to (or ill-suited to) which combination of modules.
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Program: Alzheimer's Disease
Award Type: Pilot
$149,880
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Carmen Westerberg, Ph.D.
Northwestern University
Evanston, IL
Title:
Connections Between Memory Dysfunction and Sleep in Alzheimer's Disease
Non-Technical Title:
Does Poor Sleep Contribute to Poor Memory in Alzheimer's Disease?
Duration:
April 1, 2008 - June 15, 2010
Mentor:
Ken Paller, Ph.D.
Northwestern University
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Summary: The proposal aims to investigate whether mild cognitive impairment (MCI) is associated with sleep deficits greater than expected due to those accompanying aging alone. It will assess whether sleep performance will predict performance on a test of declarative memory for items learned the day before.
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Program: Alzheimer's Disease
Award Type: Research Fellowship
$100,000
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Michael Wolfe, Ph.D.
Brigham and Women's Hospital
Boston, MA
Title:
Gamma-Secretase Modulators for Alzheimer's Disease
Non-Technical Title:
Selective Amyloid-Lowering Agents for Alzheimer's Disease
Duration:
April 1, 2010 - March 31, 2013
Co-Investigator(s):
Corinne Augelli-Szafran,
Brigham and Women's Hospital
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Summary: All of the specific aims in this research address one main goal: to identify gamma-secretase modulating drugs that are efficacious in a standard Alzheimer’s disease transgenic animal model and suitable for pre-clinical drug development. The ultimate goal is to identify a drug candidate for the treatment of Alzheimer's disease.
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Program: Alzheimer's Disease
Award Type: Standard
$400,000
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Xuemin Xu, Ph.D.
The University of Tennessee, College of Veterinary Medicine
Knoxville, TN
Title:
Vascular Risk Factors In Alzheimer's Disease
Non-Technical Title:
How Heart Disease Risk Factors Cause Alzheimer's Disease
Duration:
April 1, 2009 - March 31, 2012
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Summary: The proposed study investigates the mechanism by which oxidized lipids up-regulate the expression of Beta-secretase, which is a key enzyme in the generation of amyloid-beta from amyloid precursor protein (APP). Amyloid beta is the key molecule in the development of Alzheimer’s disease (AD) in both test-tube and living systems. The success of the proposed study will provide novel insight into the roles of oxidized lipids, the major vascular risk factors, in the development of amyloidogenesis as well as their direct neurotoxicities. The information may lead to the identification of novel therapeutic targets for preventing and curing oxidative stress-induced neurodegenerative diseases.
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Program: Alzheimer's Disease
Award Type: Standard
$400,000
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Huaxi Xu, Ph.D.
Sanford-Burnham Medical Research Institute’
La Jolla, CA
Title:
Roles of a novel gene FG01 in inhibiting Alzheimer's amyloid and tau pathologies and GSK3 activity
Non-Technical Title:
Identification and characterization of a novel gene that inhibits Alzheimer's amyloid and tau pathology
Duration:
April 1, 2008 - March 31, 2011
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Summary: This investigator has discovered a novel gene, FG01, that can significantly reduce ABeta by interfering with gamma secretase. However, this is accomplished without side effects caused by inhibiting other gamma-secretase activities. This project will continue to characterize the functions of this gene to understand its mechanism of action, and may eventually be applied to develop therapeutic interventions specifically inhibiting ABeta without unwanted side-effects.
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Program: Alzheimer's Disease
Award Type: Standard
$400,000
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Kristine Yaffe, M.D.
University of California, San Francisco
San Francisco, CA
Title:
Glucose Regulation, Cognitive & Brain Changes in Elders
Non-Technical Title:
The Effects of Diabetes and Markers of Glucose Control on Cognitive Aging
Duration:
April 1, 2010 - March 31, 2013
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Summary: By conducting our study aims, we will greatly advance our understanding of how diabetes and glucose regulation affect cognitive and brain aging. In addition, we will investigate several possible mechanisms linking diabetes to cognitive impairment. In so doing, we hope to identify strategies for prevention of cognitive decline among those with and at risk for diabetes.
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Program: Alzheimer's Disease
Award Type: Standard
$394,755
