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Takahisa Kanekiyo, M.D., Ph.D.
Washington University, School of Medicine
St. Louis, MO
Title:
LRP1 In Amyloid Beta Metabolism And CAA
Non-Technical Title:
Role Of A Receptor In Amyloid Beta Deposition On Brain Vessels
Duration:
April 1, 2009 - March 31, 2011
Mentor:
Guojun Bu, Ph.D.
Washington University
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Summary: Mounting pathological studies from Alzheimer’s disease patients have shown that amyloidbeta deposits are found not only in senile plaques but also in cerebral blood vessel as cerebral amyloid angiopathy (CAA), a major cause of intracranial hemorrhage and progressive dementia in elderly population. Amyloid beta deposition in CAA is detected primarily in the smooth muscle layer of cerebral arteries. The low-density lipoprotein receptor-related protein 1 (LRP1), known as amyloidbeta scavenger receptor, is abundantly expressed in smooth muscle cells. Therefore, the specific aims are designed to provide a comprehensive assessment of the function of LRP1 in amyloid beta metabolism and in CAA pathogenesis as well as the effect of amyloid beta on LRP1 expression and function in smooth muscle cells.
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Program: Alzheimer's Disease
Award Type: Research Fellowship
$100,000
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David Kang, Ph.D.
University of California, San Diego
La Jolla, CA
Title:
Novel Domain of LRP Cytoplasmic Tail in APP Processing
Non-Technical Title:
Blocking formation of Abeta by inhibitiing APP transport
Duration:
April 1, 2007 - March 31, 2011
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Summary: We hypothesize that the LRP-C37 domain plays a critical role in transporting LRP and APP to compartments where Ab is normally generated. In this application, we propose to characterize the mechanistic basis of the LRP-C37 domain in LRP and APP transport inside cells and Ab generation. In addition, we will determine the role of the two new LRP-C37 interacting proteins in these processes.
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Program: Alzheimer's Disease
Award Type: Standard
$400,000
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Tae-Wan Kim, Ph.D.
Columbia University
New York, NY
Title:
Modulation of BACE1 by a Novel Sorting Nexin
Non-Technical Title:
BACE1 Trafficking and Alzheimer's Disease
Duration:
April 1, 2008 - March 31, 2011
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Summary: This study will investigate the mechanism underlying the regulation of BACE1 trafficking and beta-amyloid generation in neurons by a novel sorting nexin. Gaining insight into these cellular mechanisms will lead to development of novel therapeutic approaches for preventing or treating AD.
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Program: Alzheimer's Disease
Award Type: Standard
$265,000
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Frank LaFerla, Ph.D.
University of California, Irvine
Irvine, CA
Title:
BDNF-mediated treatment for neurodegenerative disease
Non-Technical Title:
Stem cells as a treatment option for Alzheimer's disease
Duration:
April 1, 2010 - March 31, 2013
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Summary: We will explore the therapeutic benefit of using neurotrophins to treat the cognitive decline that characterizes Alzheimer’s disease. We have generated a significant body of preliminary data that show that animal neural stem cells improve function in two mouse models of Alzheimer’s disease, including one with extensive neurodegeneration. The outcome of the proposed studies will test whether neurotrophins, a factor naturally secreted by neural stem cells, can replicate the effects produced by stem cell transplantation. If this is the case, neurotrophin supplementation would provide a very promising pharmacological approach to Alzheimer’s disease that avoids any untoward effects associated with “cell-based therapies”, including stem cell transplants.
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Program: Alzheimer's Disease
Award Type: Standard
$400,000
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James Lah, M.D., Ph.D.
Emory University
Atlanta, GA
Title:
Targeted Discovery of LR11/SorLA-Based AD Therapeutics
Non-Technical Title:
Drug Discovery for Alzheimer's Disease
Duration:
April 1, 2007 - March 31, 2010
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Summary: We propose to initiate a search for LR11-interacting compounds, which will produce leads in the development of new therapeutic agents. To accomplish this, we will combine our scientific expertise with the capabilities of the NIH-funded Emory Molecular Libraries Screening Center to develop tools to identify and evaluate candidate compounds that interact with LR11.
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Program: Alzheimer's Disease
Award Type: Standard
$300,000
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Bruce Lamb, Ph.D.
The Cleveland Clinic Foundation
Cleveland, OH
Title:
Microglia , CX3CR1and Alzheimer's Disease Pathogenesis
Non-Technical Title:
Activation of the immune system in AD
Duration:
April 1, 2007 - March 31, 2011
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Summary: The focus of the current proposal is to determine the role of CX3CR1 plays in activation of the immune system, neuronal cell death and Aß deposition in two different mouse models of AD as well as to gain insight into the mechanisms involved. The long-term goal of this project is to gain insight into the role inflammation play in AD and thus provide potential new avenues of therapeutic intervention.
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Program: Alzheimer's Disease
Award Type: Standard
$400,000
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Min Jae Lee, Ph.D.
Harvard Medical School
Boston, MA
Title:
Role of Usp14 in degradation and aggregation of Tau
Non-Technical Title:
Beneficial effects of enhanced degradation of tau proteins through Usp14 inhibition
Duration:
April 1, 2010 - March 31, 2012
Mentor:
Daniel Finley,
Harvard Medical School
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Summary: The goal of this project is to understand the role of Usp14, an endogenous inhibitor of natural protein breakdown machinery, in tau protein degradation and aggregation. Successful results from this project may reveal Usp14 as a novel preventive and therapeutic target for Alzheimer’s disease, whose inhibitors are expected to facilitate the clearance of toxic, aberrant tau aggregates.
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Program: Alzheimer's Disease
Award Type: Research Fellowship
$100,000
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Malcolm Leissring, Ph.D.
Mayo Clinic Jacksonville
Jacksonville, FL
Title:
Catabolism Of Amyloid Beta And Tau By Cathepsin D In Vivo
Non-Technical Title:
Can Alzheimer Disease Be Treated With The Enzyme Cathepsin D?
Duration:
April 1, 2009 - March 31, 2012
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Summary: We have discovered that deletion of an enzyme known as cathepsin D (CatD) in mice results in very large and very selective increases in the two toxic protein species that are most closely linked to two characteristics of Alzheimer's disease (AD): (1) the amyloid beta-protein (specifically the 42-amino acid form, amyloid beta42), which deposits in the extracellular "plaques" that characterize AD, and (2) the microtubule-associated protein, tau, which makes up the neurofibrillary tangles that form inside neurons in AD and other diseases. We hypothesize that CatD plays a protective role in preventing AD by (directly or indirectly) breaking down amyloid beta42 and tau. We will test this hypothesis by increasing or decreasing CatD levels in mice that accumulate either amyloid beta 42 or tau.
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Program: Alzheimer's Disease
Award Type: Standard
$400,000
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Alan Lerner, M.D.
University Hospitals of Cleveland
Cleveland, OH
Title:
Teen IQ, Activity Level, and AD: Mechanisms of the Links
Non-Technical Title:
Duration:
April 1, 2006 - June 30, 2010
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Summary:
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Program: Alzheimer's Disease
Award Type: Pilot
$85,500
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Ling Li, Ph.D.
University of Minnesota
Minneapolis, MN
Title:
A Novel Role of ApoA-I in Alzheimer's Disease
Non-Technical Title:
Potential Role of a Heart-Protective Protein in Alzheimer's Disease
Duration:
April 1, 2010 - March 31, 2012
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Summary: Emerging evidence indicates that Alzheimer's disease and cardiovascular disease share common risk factors and pathogenic mechanisms. Human apoA-I is a major cardio-protective protein but its role in the brain pertinent to Alzheimer's disease has not been defined. This study will use a combination of behavioral, biochemical, and electrophysiological approaches to investigate the role of human apoA-I in the development of Alzheimer’s disease-like behavior and neuropathology in a mouse model of Alzheimer's disease.
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Program: Alzheimer's Disease
Award Type: Pilot
$150,000
