A New Study to Rescue Memory Impairments in Alzheimer’s Disease by Changing a Cellular Signaling Pathway

Tao Ma, MD, PhD
New York University (New York, NY)
Year Awarded:
2013
Grant Duration:
July 1, 2013 to December 31, 2015
Disease:
Alzheimer's
Award Amount:
$100,000
Grant Reference ID:
A2013030F
Award Type:
Postdoctoral Fellowship
Award Region:
US Northeastern

Reversing Alzheimer’s Disease-associated Impairments of Synaptic Plasticity and Memory by Targeting AMP-activated Protein Kinase

Mentors

Eric Klann, Ph.D.
New York University

Summary

Currently, more than five million Americans have Alzheimer’s disease (AD), and the number is estimated to rise dramatically in the next few decades. Unfortunately, until now, there is no therapy or drug available to cure or slow down the process of AD. In this study, Dr. Ma will determine the role of an important signaling pathway (5' AMP-activated protein kinase or AMPK) in the development and progression of AD, and potentially translate these discoveries into novel therapeutic targets for AD and related cognitive syndromes.

Details

There are three specific aims in this study. In the first aim, Dr. Ma is studying brain samples donated by deceased human AD patients, as well as brain samples from established mouse models of AD. This data should provide details on how AMPK and its associated signaling pathways are regulated in AD. The second and third specific aims focus on determining how restoring abnormal AMPK signaling improves AD-associated learning and memory defects, including impairments of “synaptic plasticity” (chemical and physical changes in the connections between nerve cells).

In the second aim, both drugs (small molecule inhibitors) and genetics (genetically engineered mice) are being used to determine whether AD-related deficits of long-term potentiation (LTP) or long-term depression (LTD), two primary forms of “synaptic plasticity,” can be rescued by normalizing AMPK signaling. In the third aim, two behavioral tasks widely used to assess performance of memory are being used to determine how memory deficits in AD can benefit from restoration of AMPK signaling.

Current disease-modifying strategies in clinical trials mostly focus on lowering levels of brain beta-amyloid (Abeta), and have had limited success. It is clearly urgent and necessary to identify alternative therapeutic targets to cure AD. Dr. Ma’s project incorporates multiple approaches, including many state-of-the-art techniques, to investigate in detail an Abeta-independent treatment for Alzheimer’s disease.

When this study is complete it will offer significant insights into the very core of the processes involved with Alzheimer’s disease that may be translated into developing novel therapies for this devastating disease. Dr. Ma and his team are thrilled to be part of the development, and can not sufficiently express their gratitude to those willing to support this work.
 

About the Researcher

Dr. Ma received his Ph.D. in Neuroscience from Mount Sinai School of Medicine at New York in 2008, working with Drs. Robert Blitzer and Emmanuel Landau. From 2008-2010, he was a postdoctoral research fellow with Dr. Gunnar Gouras in the Department of Neurology and Neuroscience at Weill Cornell Medical College of Cornell University. Currently, he is an Assistant Research Scientist in the laboratory of Dr. Eric Klann at the Center for Neural Science of the New York University. He has been working on the cellular/molecular mechanisms underlying neurodegenerative diseases, with a focus on Alzheimer’s disease (AD). His primary techniques include electrophysiology, confocal microscopy, behavioral tests, and molecular approaches in transgenic mouse models. He is a member of the Society for Neuroscience, the New York Academy of Sciences. He serves as Ad hoc reviewer for many neuroscience journals including “The Journal of Neuroscience” and “Neuroscience”. He has won numerous awards, including three times winner of "Young investigator scholarship" from Alzheimer's Drug Discovery Foundation, first place winner on the New York University Center of Excellence on Brain Aging Research Day, and Fellowship Grant from Alzheimer’s Association International Conference. He has a well-established publishing record in leading peer-review journals, with many articles featured by the journals and/or reported in media. He has frequently given oral presentations at scientific meetings such as the Society for Neuroscience Annual Meeting and the Alzheimer’s Association International Conference.