Profiling Structure and Biology of Beta Amyloid Strains

About the Research Project
Program
Award Type
Standard
Award Amount
$275,529
Active Dates
July 01, 2016 - June 30, 2019
Grant ID
A2016085S
Co-Principal Investigator(s)
Quingzhong Kong, PhD, Case Western Reserve University
Mentor(s)
Quingzhong Kong, PhD, Case Western Reserve University
Goals
We believe our project addresses a confounding puzzle: Why clinical symptomatology, severity, and progression rates of late-onset Alzheimer disease (AD) frequently do not coincide with the total beta amyloid (Aβ) load? We propose to test the hypothesis that rapid progression of the disease is caused by specific molecular structural features of Aβ. The findings have the potential to significantly improve our understanding of AD and to establish progression rate-directed diagnostics and therapeutic interventions as a key strategy for delaying and preventing symptomatic AD.
Summary
The findings generated in this project have a potential to significantly improve our understanding of Alzheimer diseases (AD) and to establish transgenic mice models of Alzheimer’s disease (AD) replicating important characteristics of human disease. Such models are critical for the development of progression rate-directed diagnostics and therapeutics. We also anticipate that translating the methods developed for molecular characterization of brain Aβ will significantly improve the predictive value, specificity, and sensitivity of plasma and cerebrospinal fluid (CSF) tests for AD and provide the basis for individual risk assessment and therapeutic monitoring. Moreover, the new data generated in this proposal provide a foundation for long term advanced structural studies of brain Aβ and the mechanism(s) of accumulation in the brain. Finally, improved understanding of the molecular mechanism responsible for different progression rates of the disease should translate to the design of new structure-based therapeutic interventions with the potential to slow down AD progression as a key strategy for delaying and ultimately preventing symptomatic stages of the disease.
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