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Mark Girvin, Ph.D.
Albert Einstein College of Medicine of Yeshiva University
Bronx, NY
Title:
Structural Determinants for Bri2 Inhibition of A-beta Production
Non-Technical Title:
Structure of a natural inhibitor of amyloid-beta production
Duration:
April 1, 2008 - March 31, 2010
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Summary: This project seeks to determine the molecular structure of BRI2, a molecule that protects APP from being cleaved to produce amyloid beta. By comparing the structure of BRI2 when it is free to its structure when bound to APP, this study will highlight components of the protein that might serve as targets in future drug design.
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Program: Alzheimer's Disease
Award Type: Pilot
$150,000
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Alison Goate, D.Phil.
Washington University
St. Louis, MO
Title:
Identification of functional alleles that influence cerebrospinal fluid levels of Aß and risk for Alzheimer's disease
Non-Technical Title:
Searching for genetic variation that influences cerebrospinal fluid protein levels and risk for Alzheimer's disease
Duration:
April 1, 2008 - March 31, 2011
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Summary: Comparisons of levels of A Beta peptides found in the cerebrospinal fluid can be used to predict the risk of developing Alzheimer's disease. By searching for genes that perturb the ratios of ABeta levels in the CSF this proposal seeks to identify new genes involved in the development of late onset Alzheimer's disease.
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Program: Alzheimer's Disease
Award Type: Standard
$400,000
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Francine Grodstein, Sc.D.
Harvard University
Boston, MA
Title:
Mid-life Telomere Length and Cognitive Decline in Later Life
Non-Technical Title:
Markers of Aging at Mid-life and Memory at Older Ages
Duration:
April 1, 2008 - March 31, 2010
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Summary: Previous studies have provided suggestive evidence for an association between telomere length and cognitive function. This study aims determine whether telomere length might predict status of cognitive decline 10 years later by analyzing data from the Nurses' Health Study.
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Program: Alzheimer's Disease
Award Type: Pilot
$100,000
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Ping He, M.D., Ph.D.
Sun Health Research Institute
Sun City, AZ
Title:
Regulatory Mechanism of BACE by Inflammatory Factors
Non-Technical Title:
Regulatory Mechanism of BACE by Inflammatory Factors
Duration:
April 1, 2008 - March 31, 2010
Mentor:
Yong Shen, M.D., Ph.D.
Sun Health Research Institute
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Summary: This study will test BACE mRNA levels and protein activity in autopsied brains from Mild Cognitive Impaired patients. This study will also test whether TNFAlpha pathway can induce BACE protein synthesis and transcription in cell culture.
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Program: Alzheimer's Disease
Award Type: Research Fellowship
$100,000
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Joachim Herz, M.D.
The University of Texas Southwestern Medical Center at Dallas
Dallas, TX
Title:
An Apoe Receptor-Mediated Mechanism For AD Pathogenesis
Non-Technical Title:
Apoe Receptors In Alzheimer's Disease
Duration:
April 1, 2009 - March 31, 2012
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Summary: We have identified a novel conceptual mechanism by which ApoE and amyloid beta peptide interact at the level of the synapse. This mechanism has the potential to explain the fundamental molecular pathways that underlie the causes of Alzheimer's disease. Understanding of these mechanisms may open a new door to effective, rational drugs designed to work against Alzheimer's disease.
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Program: Alzheimer's Disease
Award Type: Standard
$400,000
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George Jackson, M.D., Ph.D.
University of California, Los Angeles
Los Angeles, CA
Title:
Validation and Characterization of Tau Modifiers In Vivo
Non-Technical Title:
Examining regulation of tau protein
Duration:
April 1, 2007 - March 31, 2010
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Summary: These experiments propose further studies of the role of PSA in tauopathy, and plan to validate other genes identified as putative protective or susceptibility genes in the transgenic human tau P301L mouse model.
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Program: Alzheimer's Disease
Award Type: Standard
$400,000
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Thomas Jongens, Ph.D.
The Trustees of the University of Pennsylvania
Philadelphia, PA
Title:
Testing For Calcium Dysregulation In A New AD Model
Non-Technical Title:
Determining If Calcium Levels Are Linked To Loss Of Mental Abilities
Duration:
April 1, 2009 - March 31, 2011
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Summary: One hypothesis, put forth by several investigators, is that dysregulation of intracellular calcium is an early or central cause of at least some of the symptoms of Alzheimer's disease. In the experiments outlined in this proposal we will determine if the misregulation of intracellular calcium levels is linked to the age of onset of cognitive deficits that we observe in a new Drosophila (fruit fly) model for Alzheimer's disease that is based on loss of presenilin activity.
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Program: Alzheimer's Disease
Award Type: Pilot
$150,000
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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, 2010
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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
