Using Emerging Technologies to Identify the Effects of ApoE in the Brain

Tal Nuriel, PhD
Columbia University Medical Center (New York, NY)
Year Awarded:
2014
Grant Duration:
July 1, 2014 to June 30, 2016
Disease:
Alzheimer's
Award Amount:
$120,000
Grant Reference ID:
A2014200F
Award Type:
Postdoctoral Fellowship
Award Region:
US Northeastern

Co-principal Investigators

Karen W Duff, Ph.D.
Columbia University Medical Center
Steven Gross, PhD (Mentor)
Weill Cornell Medical College
This grant is made possible in part by a bequest from the Louise T. Baker Trust.

Metabolomic/Lipidomic Analysis of ApoE Isoform Effects

Mentors

Multiple mentors, listed above

Summary

The apolipoprotein E (apoE) gene controls a small protein that helps clear cholesterol and other fats though the bloodstream. For some time, Alzheimer’s researchers have focused on a variation of the apoE gene known as the “E4” allele. Carriers of the apoE4 mutation are at significantly increased risk for developing late-onset Alzheimer’s disease. In order to understand the cause of this increased Alzheimer’s risk, we will utilize emerging technology to measure the levels of lipids and small-molecules in mouse and human brain tissues possessing differing forms of apoE. We anticipate that the results of this study will shed new light on why apoE4 carriers are more susceptible to Alzheimer’s disease and how Alzheimer’s disease can be prevented in these individuals.

Details

The goal of this project is to discover new molecules that are affected by expression of the apoE4 gene and that may play a role in the increased risk of Alzheimer’s disease among apoE4 carriers.

In order to do this, we will use emerging technology known as “omics” to identify lipids and small molecules in the brain that are affected by the expression of differing forms of apoE. Using this technology, we will be able to observe hundreds of lipids and thousands of small-molecules in order to identify the specific molecules that either increase or decrease when different forms of apoE are expressed. We will then utilize additional biochemical techniques to discover whether these changes are involved in the increased risk for Alzheimer’s disease that occurs among apoE4 carriers.

This project will be the first to utilize multiple versions of this “omics” technology to investigate the potential mechanisms responsible for the link between apoE4 and Alzheimer’s disease. Importantly, we anticipate that the results of this study will not only shed light on the role of apoE4 in Alzheimer’s disease, but may also point to previously undiscovered processes involved in the development of Alzheimer’s disease.

Although numerous clinical trials for Alzheimer’s disease are currently under way, most are aimed at preventing or eliminating the two main hallmarks of Alzheimer’s disease, amyloid plaques and neurofibrillary tangles. By uncovering new processes involved in the increased risk of Alzheimer’s disease among apoE4 carriers, we hope that this study will identify new therapeutic targets that will increase our chances of finding a successful treatment for Alzheimer’s disease in the near future.

About the Researcher

Tal Nuriel is a postdoctoral research fellow at the Columbia University Medical Center (CUMC). He earned his bachelor's degree at the University of Michigan where, as part of the university's Undergraduate Research Opportunities Program, he worked in the Brain Tumor Research Laboratory. Next, Dr. Nuriel worked for three years as a research technician in the laboratory of Moses Chao,PhD, at New York University's Skirball Institute of Biomolecular Medicine, where he focused on multiple sclerosis and other neuropathological disorders. Dr. Nuriel then began his graduate work at Weill Cornell Medical College, where he worked in the laboratory of Steven Gross, PhD, focusing mainly on proteomics and developing novel applications to identify protein modifications caused by oxidative and nitrosative stress in disorders such as Alzheimer's disease. During his time in Dr. Gross’s laboratory, Dr. Nuriel published numerous research articles and was awarded an F31 NRSA fellowship from the National Institute on Aging. After graduate school, he decided to focus his energies on understanding the mechanisms and potential treatments of Alzheimer's disease, and was excited to receive a postdoctoral position at CUMC in the laboratory of Karen Duff, PhD, a recognized leader in the Alzheimer's field. Currently, in her laboratory, Dr. Nuriel is using cutting-edge omics technology (a new biological field aimed at charting the role of molecules within organisms) to understand the role of the apoE4 protein in promoting Alzheimer's disease. By performing the experiments outlined in this grant, Dr. Nuriel hopes to make significant contributions to the Alzheimer's field that will increase our chances of finding effective treatments for Alzheimer's disease in the near future.