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Paul H. Axelsen, M.D.
University of Pennsylvania
Philadelphia , PA, United States
Title:
Oxidative Lipid Degradation in Alzheimer's Disease
Non-Technical Title:
Oxidative Stress in Alzheimer's Disease
Duration:
July 1, 2011 - June 30, 2013
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Summary: Oxidative stress will be examined in animal models of Alzheimer's disease using novel radiolabeled compounds that are designed to reveal how the proteins that accumulate in Alzheimer's disease are induced to form fibrils and plaques.
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Program: Alzheimer's Disease
Award Type: Standard
$250,000
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Kiran Bhaskar, Ph.D.
Lerner Research Institute at Cleveland Clinic
Cleveland, OH, United States
Title:
Role of p38 MAPK in the Microglial-Mediated Alzheimer's Disease Tau Pathology
Non-Technical Title:
The Role of p38 MAPK as a Putative Drug Target Against Alzheimer's Disease Tangle Pathology
Duration:
July 1, 2011 - June 30, 2013
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Summary: In a recent study (published in October 7th, 2010 issue of the journal NEURON), we have identified p38 MAPK as a link between neuroinflammation, cell-autonomous to microglia, and Alzheimer's disease tau pathology. In the current study, the role of a safe, orally bioavailable and brain permeable p38 MAPK inhibitor (MW01-2-069A-SRM) in preventing tau pathology will be examined both in vitro utilizing primary neurons and in vivo utilizing a unique transgenic mouse model of tauopathy (hTau mice).
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Program: Alzheimer's Disease
Award Type: Pilot
150,000
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Narayan Bhat, Ph.D.
Medical University of South Carolina
Charleston, SC, United States
Title:
Role of a Stress Kinase in AD Pathogenesis
Non-Technical Title:
Defining the Role of a Signaling Pathway in Alzheimer's Disease
Duration:
July 1, 2011 - June 30, 2014
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Summary: The project investigates the role of a key cell signaling pathway commonly involved in cell stress and inflammatory responses i.e., p38 MAP kinase in multiple pathogenic processes of Alzheimer's disease (AD) including neuroinflammation, tau phosphorylation, amyloid deposition and synaptic dysfunction. The approach uses a genetic conditional knockout strategy to cell-specifically delete the kinase in microglia and forebrain neurons in a mouse model of AD. The outcome will provide mechanistic insight into AD-associated pathogenic processes and define the signaling pathway as a versatile treatment target for AD.
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Program: Alzheimer's Disease
Award Type: Standard
$399,873
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Kurt R. Brunden, Ph.D.
University of Pennsylvania
Philadelphia, PA, United States
Title:
In Vivo Testing of Novel Tau Fibrillization Inhibitors
Non-Technical Title:
Inhibiting Formation of Alzheimer's Disease Pathology
Duration:
July 1, 2011 - June 30, 2013
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Summary: The accumulation of insoluble fibrils of tau protein within neurons is a hallmark pathological feature of the Alzheimer's disease brain. A body of evidence suggests that these tau fibrils are pathogenic and contribute to the neuron loss observed in Alzheimer's disease. The research proposed here is to further characterize novel drug-like inhibitors of tau fibril formation, and the results of these studies will provide important information about the therapeutic potential of such compounds for the treatment of Alzheimer's disease.
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Program: Alzheimer's Disease
Award Type: Pilot
150,000
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Guojun Bu, Ph.D.
Mayo Clinic
Jacksonville, FL, United States
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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Paramita Chakrabarty, Ph.D.
University of Florida
Gainesville, FL, United States
Title:
Soluble Toll-Like Receptors: Potential Anti Amyloid Beta Agents
Non-Technical Title:
Expressing Engineered Receptor Domains to Treat Alzheimer's Disease
Duration:
July 1, 2011 - June 30, 2012
Mentor:
Todd Golde, M.D., Ph.D.
University of Florida at Gainesville
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Summary: Histopathological evidence establishes a link between neuroinflammation and senile amyloid beta plaques found in the brains of Alzheimer's disease (AD) patients. It has been proposed that continued neuroinflammation causes bystander toxicity and neuronal death in AD patients. Toll-like receptors have been reported to be critical components of the immune system that drives brain inflammation. In this study, we propose to express parts of Toll-like receptors which would still be able to bind and sequester the amyloid beta peptides without causing sustained neuroinflammation. Such engineered receptors may yield promising therapeutic interventions targeting amyloid pathology. Such receptors have been used in mouse models to target systemic diseases like arthritis and tumor therapy.
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Program: Alzheimer's Disease
Award Type: Research Fellowship
$49,528
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Biju K. Chandu, Ph.D.
The University of Texas Health Science Center at San Antonio
San Antonio, TX, United States
Title:
iPS-Derived Microglia-Based Gene Therapy for Alzheimer's
Non-Technical Title:
A New Therapy Using Stem Cells to Halt or Reverse the Course of Alzheimer's Disease
Duration:
July 1, 2011 - June 30, 2013
Co-Investigator(s):
Senlin Li, M.D. (Mentor)
University of Texas Health Science Center
Robert A. Clark, M.D. (Mentor)
University of Texas Health Science Center
Mentor:
Multiple mentors, listed above.
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Summary: Extracting bone marrow cells requires surgery, which may be strenuous or impossible for older patients. To meet large scale demand of bone marrow cells in clinical for the treatment of Alzheimer's disease, we will generate bone marrow cells from blood, which we in turn genetically modify to secrete drugs once these cells migrate to the brain. This new approach is expected to contribute to the development of an important therapy for Alzheimer's.
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Program: Alzheimer's Disease
Award Type: Research Fellowship
$100,000
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Allen C. Chen, Ph.D.
Brigham and Women's Hospital
Boston, MA, United States
Title:
Association Among the Secretases: Model of APP Cleavage
Non-Technical Title:
Interaction Between the Secretases: A New Model of APP Processing
Duration:
July 1, 2011 - June 30, 2012
Mentor:
Dennis J. Selkoe, M.D.
Brigham and Women's Hospital, Harvard Medical School, Boston, MA
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Summary: The goal of this proposal is to validate and confirm a functional complex of alpha (and also beta)-secretase with gamma-secretase. The hypothesis is that alpha- and gamma-secretase associate together in a larger complex that is able to accept full-length substrates and process them rapidly and sequentially. I will rigorously and meticulously characterize this complex both structurally and functionally.
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Program: Alzheimer's Disease
Award Type: Research Fellowship
$50,411
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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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Marta Cortes-Canteli, Ph.D.
Rockefeller University
New York , NY, United States
Title:
Role of Fibrinogen in AD Neuronal and Synaptic Loss
Non-Technical Title:
Blood Circulation and Neuronal Health in the Alzheimer's Brain
Duration:
July 1, 2011 - June 30, 2013
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Summary: The association between fibrinogen and Abeta affects normal hemostasis. Determining if fibrinogen also influences the neuronal and synaptic loss present in Alzheimer's disease is substantially important as it will support the design of therapeutic strategies aimed at blocking that association.
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Program: Alzheimer's Disease
Award Type: Pilot
$150,000
