Congratulations OPAR Grant Recipients!
The Oregon Partnership for Alzheimer's Research Committee (OPAR) is pleased to announce the recipients of the 2010-2011 OPAR grants. These grants are made possible through the Oregon Tax Checkoff program. You can support this program when you file your state income tax. The Fund supports researchers who are entering the field of Alzheimer's disease research or who are pursuing new directions in Alzheimer's research.
Thimmappa S. Anekonda, Ph.D. OHSU Assistant Professor, Neurology
"Phytic acid for early treatment of amyloid beta pathology"
Intra-neuronal accumulation of soluble form of amyloid beta oligomer is an early hallmark of AD. This study proposes a novel protective treatment for Alzheimer's disease with phytic acid, a plant chemical found in food grains. Phytic acid treatment may attenuate oxidative stress and promote cellular housekeeping functions. Using the transgenic mouse model of AD and age-matched wild-type mice, this study will provide crucial data on the effectiveness of phytic acid against AD, and help prepare NIH proposals for additional funding.
Bonnie Bolkan, Ph.D. OHSU Post-doctoral fellow, CROET
"Functional and molecular characterization of BACE in Drosophila"
The presence of Beta-Amyloid containing plaques in the brain is one of the histological hallmarks of AD. Beta-Amyloid is a cleavage product of Amyloid Precursor Protein (APP), which is cut by gama-secretase and either alpha-secretase or beta-secretase (BASE). Together, the beta and gamma cleavage leads to the toxic Beta-Amyloid. Due to its integral role in making this toxic peptide, BACE has become a major focus for inhibitory drugs to treat Alzheimer's. The goal of this research is to gain information by using the fruit fly as a model organism. Fruit flies provide a simple organism in which to study BACE's function, but retains enough similarity to humans that the fruit fly BACE is able to cut the human form of APP as well as the fruit fly ortholog, APPL. Understanding the function of as well as the interaction of BACE with other proteins will provide additional information towards the suitability of therapeutically inhibiting BACE in addition to other potential options for future drug targets.
Catherine Drerup, Ph.D. OHSU Post-doctoral fellow, Cell and Developmental Biology
"JNK-dependent modulation of APP axonal transport"
This study will allow analyses of the transport of Amyloid Precursor Protein (APP) in an intact vertebrate animal. We will analyze the axon transport of APP and APP cleavage products in an intact zebrafish embryo. In addition we will determine how phosphorylation of APP affects its transport dynamics. These analyses will shed light on the endogenous movement of APP in a functioning neural circuit and how modification of phosphorylation status of the protein impacts this process. The information gained will contribute to understanding of the function of APP and provide insight into the cellular mechanisms which, when disrupted, may predispose individuals to developing AD.
Julia V. Perederiy OHSU Graduate student, Vollum Institute
"Peripheral administration of IGF-1 accelerates maturation and integration of newborn granule cells in the adult dentate gyrus"
The purpose of this study is to gain understanding about the capability of the nervous system to self-repair in diseases such as Alzheimer's. Neuronal precursors in the dentate gyrus divide continuously throughout life, and upon differentiation, mature into functional neurons and integrate into the surrounding circuitry. Interestingly, proliferation and survival of these cells is enhanced following exercise, an effect that is mimicked by elevated systemic levels of circulating insulin-like growth factor 1 (IGF-1), suggesting that this endogenous, liver-derived growth factor may mediate the neurotrophic effects of physical activity. In this study, using a unique transgenic mouse in which newborn granule cells can be easily identified via fluorescence, tests the hypothesis that IGF-1 enhances survival of granule cells by accelerating the maturation and functional integration into existing hippocampal circuitry.