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Paul Axelsen, M.D.
University of Pennsylvania
Philadelphia, PA
Title:
Oxidative stress and amyloidogenesis
Non-Technical Title:
The chemistry of Alzheimer's disease
Duration:
April 1, 2008 - September 30, 2010
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Summary: Oxidative stress and amyloid fibril formation are consistent major themes among processes thought to be involved in the pathogenesis of Alzheimer's disease. However, a mechanistic link between these two processes has not been defined. The research being proposed will probe human brain tissues and animal models of Alzheimer's disease for evidence of a specific chemical mechanism that will be amenable to therapeutic intervention.
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Program: Alzheimer's Disease
Award Type: Pilot
$187,500
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Guojun Bu, Ph.D.
Washington University, School of Medicine
St. Louis, MO
Title:
RP1 and Insulin Receptor Signaling in AD
Non-Technical Title:
Lipoprotein receptor and insulin signaling in Alzheimer's disease and type II diabetes
Duration:
April 1, 2010 - March 31, 2013
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Summary: Insulin resistance is a risk factor for Alzheimer’s disease (AD) and apoE receptor LRP1 plays critical roles in AD pathogenesis. We intend to dissect how LRP1 and insulin receptors cooperate in regulating the metabolism and toxicity of amyloid beta peptide, which is central to AD. Our work should provide critical knowledge regarding why insulin resistance and type II diabetes are risk factors for AD.
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Program: Alzheimer's Disease
Award Type: Standard
$400,000
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Catherine Clelland, Ph.D.
Columbia University
New York, NY
Title:
The Role of miR-138 in Alzheimer’s Disease Dendritic Spine Pathology
Non-Technical Title:
Exploring a novel abnormal regulatory pathway in Alzheimer’s disease brain cell connections
Duration:
April 1, 2010 - March 31, 2012
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Summary: We will test if dysregulation of the miR-138 controlled pathway contributes to dendritic spine pathology in a murine tauopathy model. We believe this project is highly innovative because if successful, this study will be one of the first to directly link the dysregulation of a miRNA regulated pathway to the in vivo dendritic spine pathology seen in a mouse model of human tauopathy.
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Program: Alzheimer's Disease
Award Type: Pilot
$150,000
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Bruce Cohen, Ph.D.
McLean Hospital
Belmont, MA
Title:
A Novel Treatment Strategy for Neurorepair in Alzheimer's Disease
Non-Technical Title:
The Use of Adult Bone Marrow Stem Cells in Treating Alzheimer's Disease
Duration:
April 1, 2008 - November 30, 2010
Co-Investigator(s):
Kai Sonntag, M.D., Ph.D.
McLean Hospital
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Summary: In this project, 'adult' stem cells will be used as a delivery system to deliver sAPP to brain regions undergoing neurodegeneration. The hypothesis is that sAPP will work together with growth factors to protect and repair cholinergic neurons in the brain, thereby representing a potential for therapeutic treatment in humans with AD.
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Program: Alzheimer's Disease
Award Type: Pilot
$150,000
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Erin Congdon, Ph.D.
Research Foundation For Mental Hygiene
New York, NY
Title:
Tau Dissociation As A Therapeutic Approach For Tauopathy
Non-Technical Title:
Untangling Tau As An Approach To Treating Tangles In AD
Duration:
April 1, 2009 - March 31, 2011
Mentor:
Karen Duff, Ph.D.
Columbia University
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Summary: Aggregated tau accumulated in tangles is a major feature of the Alzheimer’s disease affected brain. These accumulations are thought to be highly toxic to neurons. Aggregated tau can be disassociated in test tubes by several compounds including cyanine dyes. We aim to test the therapeutic potential of a cyanine dye both in living systems and in living system models of disease.
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Program: Alzheimer's Disease
Award Type: Research Fellowship
$100,000
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Marta Cortes-Canteli, Ph.D.
Rockefeller University
New York, NY
Title:
Role Of Amyloid Beta-Fibrinogen Interaction In Alzheimer's Disease
Non-Technical Title:
Blood Clots In The Alzheimer's Disease Brain
Duration:
April 1, 2009 - March 31, 2011
Mentor:
Sidney Strickland, Ph.D.
Rockefeller University
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Summary: Amyloid beta interacts with fibrinogen in test tubes and prevents fibrin clots from degrading. Studying this phenomenon in living systems in addition to the role of ApoE in disease pathology will help to clarify the role of fibrin in the abnormal cerebral vasculature in Alzheimer's disease.
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Program: Alzheimer's Disease
Award Type: Research Fellowship
$100,000
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Pritam Das, Ph.D.
Mayo Clinic Jacksonville
Jacksonville, FL
Title:
Cytokine Modulation Of Amyloid Beta Associated Pathologies In APP Mouse Models Of Alzheimer's Disease
Non-Technical Title:
Effect Of Inflammation In The Brain On Disease Progression In Alzheimer’s Disease
Duration:
April 1, 2009 - March 31, 2012
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Summary: The experiments proposed here will establish an experimental template to study potential disease modifiers, their roles in modulating Alzheimer’s disease (AD) like pathologies and their use in the future design of potential AD therapeutics.
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Program: Alzheimer's Disease
Award Type: Standard
$399,999
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Marc Diamond, M.D.
Washington University, School of Medicine
St. Louis, MO
Title:
Cell-Cell Transfer and Propagation of Tau Aggregates
Non-Technical Title:
Determination of how protein aggregates spread between cells
Duration:
April 1, 2010 - March 31, 2013
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Summary: This work addresses an overarching question of why neurodegeneration spreads inexorably through the brain. The research will address specifically how aggregates of misfolded tau protein move between cells, and whether they serve as a template that directly seeds or otherwise catalyze further aggregation.
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Program: Alzheimer's Disease
Award Type: Standard
$400,000
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Kelley Dineley, Ph.D.
University of Texas Medical Branch
Galveston, TX
Title:
PPAR-Gamma Rescue Of Cognitive Function In Alzheimer's Disease
Non-Technical Title:
Insulin Regulatory Gene In The Central Nervous System Mediates Cognitive Function In Alzheimer's Disease
Duration:
April 1, 2009 - March 31, 2012
Co-Investigator(s):
Larry Denner, Ph.D.
University of Texas Medical Branch
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Summary: Our preliminary studies have discovered a role for a gene called PPAR-gamma in cognitive function in Alzheimer's disease. Since virtually nothing is known about PPAR-gamma regulation in the brain, the specific aims of this project are to define the PPAR-gamma signaling axis in brain regions that underlie the types of cognitive function that PPAR-gamma agonism improves.
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Program: Alzheimer's Disease
Award Type: Standard
$399,000
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Jinghui Dong, Ph.D.
Tufts University School of Medicine
Boston, MA
Title:
P2Y6 Activation-mediated Clearance of Amyloid Plaque
Non-Technical Title:
Activation of P2Y6 Receptor Mediates Clearance of Amyloid Plaque in Mice Model of AD
Duration:
April 1, 2010 - March 31, 2012
Mentor:
Philip Haydon,
Tufts University School of Medicine
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Summary: Microglia express the metabotropic P2Y6 receptor, whose activation by its endogenous agonist uridine diphosphate (UDP) triggers phagocytosis in response to neuronal injury. Given that the UDP/P2Y6 receptor system functions as a sensor of phagocytosis and initiates the clearance of debris in the brain, the main research objective of this study is to test the hypothesis that activation of the P2Y6 receptor results in amyloid plaque clearance and synaptic and cognitive improvement in an animal model of Alzheimer’s disease (AD), and the PSAPP transgenic mouse.
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Program: Alzheimer's Disease
Award Type: Research Fellowship
$100,000
