Novel Factors that Regulate Alzheimer's Disease Pathology

Vivek Gautam, DVM, PhD
Massachusetts General Hospital, Harvard Medical School (Boston, MA)
Year Awarded:
2013
Grant Duration:
July 1, 2013 to June 30, 2015
Disease:
Alzheimer's
Award Amount:
$100,000
Grant Reference ID:
A2013478F
Award Type:
Postdoctoral Fellowship
Award Region:
US Northeastern

Role of Neurexins in Alzheimer's Disease

Mentors

Dora Kovacs, PhD
Massachusetts General Hospital (Charlestown, MA)

Summary

The severity of Alzheimer's disease (AD) symptoms is directly linked to levels of the amyloid beta (i.e., the generation of Abeta peptide), as shown by genetic studies. Abeta levels and the amount of amyloid deposits increase in AD, yet factors that increase Abeta levels at the synapses (the connections between nerve cells) remain largely unknown. The goal of this project is to study the role of a type of synapse protein, called Neurexins, in regulating amyloid deposition in AD. Collectively, this research proposal will provide novel insights into the development and progression of Alzheimer's disease.

Details

The laboratory of Drs. Gautam and Kovac recently identified the Neurexin family of proteins as a novel type of interacting partners for Amyloid Precursor Protein (APP), a protein that generates toxic Abeta peptide in the brain. Functional relevance of this interaction is underscored by the result that reducing the expression level of Neurexin significantly increases toxic Abeta levels in neurons. As expression of different forms of Neurexin in different brain regions is highly age-dependent, regulated interaction between APP and Neurexins may regulate synaptic Abeta generation. Here, the team of Drs. Gautam and Kovac is testing the hypothesis that Neurexin represses Abeta generation in the brain by interacting with APP in a regulated manner. For this purpose, the team is studying the mechanism of how Neurexins modulate APP metabolism and Abeta generation in cultured nerve cells. The results of these studies may help to understand the initiation and progression of Alzheimer's disease, and may contribute to the development of novel strategies for the prevention and treatment of the disease.

About the Researcher

Dr. Vivek Gautam is a Research Fellow in the Neurology department at Massachusetts General Hospital and Harvard Medical School. He did his Veterinary Medicine degree from G.B. Pant University, India and later joined University of Nebraska Medical Center for his doctoral studies in the field of Neuroscience. At Massachusetts General Hospital/Harvard Medical School, his research work focuses on the identification of novel factors that regulate Alzheimer’s disease pathogenesis.