APOE genotype-specific effects of young plasma on cerebrovasculature and AD pathology.
Project Description
Alzheimer’s disease (AD) is the leading cause of dementia in the elderly and has become a growing epidemic in our aging society. Despite tremendous progress in understanding the etiology of AD, we still do not have an effective treatment to prevent or cure this devastating disease. The APOE gene is the strongest genetic risk factor for AD because it affects multiple pathways collectively contributing to neurodegeneration and dementia. Our long-term goal is to explore APOE-targeted therapy by understanding how different forms of APOE, either in the brain or in blood circulation, affect brain functions and AD development. Our recent studies have shown that APOE4, which is associated with increased risk for AD, has detrimental effects both in the brain and in peripheral blood. Specifically, APOE4 in the blood impairs brain cognition and increases amyloid pathology likely through mechanisms impacting brain vasculature. As such, targeting APOE in the blood can be an attractive therapeutic strategy. With increasing evidence that young plasma has rejuvenating effects on brain functions, our specific goal for this project is to examine how young plasma with different forms of APOE (risky or protective) alter the integrity and function of brain blood vessels, and Alzheimer pathologies. Our specific hypothesis is that APOE genotype status impacts young plasma composition including proteins, lipids, and metabolites, leading to differential effects on brain vessel integrity and function as they relate to brain cognition and AD pathology. We plan to test our hypothesis by examining how APOE genotype-specific young plasma differentially impacts brain vessel integrity and function, as well as AD pathologies using mouse models with amyloidosis or tau pathology. Upon completion of these studies, we will have greater knowledge about how young plasma impacts brain functions and AD pathologies in an APOE genotype-specific manner. Such knowledge will guide rational design of clinical trials using young plasma from individuals with the protective forms of APOE.
Supervisor
BU, Guojun
Quota
2
Course type
UROP1100
Applicant's Roles
The applicant will assist PhD students in conducting experiments, primarily focusing on immunofluorescence staining and Western blotting. Their roles include understanding the basic principles of these experiments and performing routine experimental procedures. These experiments aim to evaluate the phenotypes of endothelial cells and the changes in specific proteins within these cells when treated with plasma from different APOE genotypes (APOE2, APOE3, or APOE4). The applicant will support sample preparation, carry out staining and Western blotting procedures, and ensure that experiments run smoothly under supervision.
Applicant's Learning Objectives
By reviewing relevant literature, the applicant will gain a foundational understanding of the structure and function of brain vasculature and how these are altered during Alzheimer’s disease. They will learn the basic principles and techniques of immunofluorescence staining and Western blotting. Under the guidance of PhD students and postdoctoral fellows in the PI lab, the applicant will develop proficiency in these techniques and independently conduct relevant experiments as appropriate. By the end of the project, the applicant will compile a report detailing the project background, research gaps, experimental objectives, methodologies, results, and conclusions.
Complexity of the project
Moderate