Alzheimer's Disease Research - Current Awards Ken A. Paller, Ph.D.Northwestern University Title: Entrainment of Slow-Wave Sleep to Improve Memory in MCI Summary: Recent findings have suggested that memory storage in the human brain depends not only on the proper acquisition of information and its later retrieval, but also on intermediate processing. Interestingly, the intermediate processing that allows memories to be stored in an enduring manner appears to depend on memory processing during sleep. Accordingly, this project investigates whether some of the memory problems experienced in Alzheimer's disease are related to inadequate memory processing during sleep, and whether such a dysfunction can be corrected through a novel electrical stimulation method. Program: Alzheimer's Disease  Angèle Parent, Ph.D.The University of Chicago Title: Functional Interaction of APP-CTF with G-alphaS in Brain Summary: Dr. Angèle Parent and her team’s research efforts focus on understanding the molecular and cellular mechanisms associated with development of Alzheimer’s disease. In this project, they are using transgenic mouse and cell culture techniques to study the function a protein that is suspected to contribute to the pathogenesis. The ultimate goal is to develop novel therapeutic strategies that are applicable to humans to fight this devastating disorder. Program: Alzheimer's Disease  Margaret A. Pericak-Vance, Ph.D.University of Miami Title: Whole Exome Sequencing in Alzheimer Disease Co-PI(s):
Stephan Zuchner, M.D., Ph.D.
University of Miami Summary: The proposed research will look for rare variants in AD in a unique set of large multigenerational AD families that have been followed by our group for over 25 years. Together with ongoing efforts of ours and others to identify common AD risk variants the whole exome approach outlined in this proposal will afford us the best chance to understand the genetic causes of AD and to determine the functional role of the genes underlying this risk. Program: Alzheimer's Disease  Alya R. Raphael, Ph.D.Stanford University Title: Stress Granule Pathways in TDP-43 Toxicity Mentor:
Aaron Gitler, Ph.D.
Stanford University Summary: Alzheimer’s disease and related neurodegenerative disease are devastating diseases that affect millions of people each year and have enormous societal costs. The pathology of many of these diseases involves the formation of insoluble protein aggregates, although whether these aggregates are the cause or result of disease is unknown. TDP-43, and the related protein FUS, are found aggregated in several neurodegenerative diseases. Understanding the biology behind their pathology may point to new treatment strategies. Program: Alzheimer's Disease  Michael Rohe, Ph.D.Max-Delbrueck Center for Molecular Medicine Title: Role of SORLA in Transport of TrkB and APP in Alzheimer's Disease Mentor:
Thomas E. Willnow, Ph.D.
Max-Delbrueck Center for Molecular Medicine Summary: Accelerated amyloidogenic processing of APP and insufficient trophic signals from BDNF are two well-documented risk factors in AD. Intriguingly, both pathways converge on yet another established AD risk gene, the neuronal sorting receptor SORLA. A more detailed understanding of how these pathways are interconnected in the healthy and in the diseased brain will provide the basis for evaluating the therapeutic potential of SORLA to reduce neurotoxicity (caused by too much Abeta) and to strengthen neurotrophic support (caused by poor BDNF signals). Program: Alzheimer's Disease  Mert R. Sabuncu, Ph.D.Massachusetts General Hospital Title: Predicting Future Alzheimer’s Disease Onset Based on MRI and Genotype Summary: Alzheimer's disease (AD), the most common form of dementia, has a multi-year pre-clinical phase, during which subtle changes begin to happen in the brain, yet clinical symptoms such as memory loss don't yet appear. This project by Dr. Mert Rory Sabuncu and colleagues will develop a computer system that analyzes brain magnetic resonance imaging (MRI) and saliva-derived DNA data in order to reliably quantify risk of Alzheimer's before memory complaints begin. This technology will provide a means to identify high-risk but healthy individuals who would benefit most from a drug that can slow down the progression of the disease. Program: Alzheimer's Disease  Ismael Santa-Maria Perez, Ph.D.Columbia University Medical Center, Taub Institute for Research on Alzheimer´s Disease and the Aging Brain Title: Role of microRNAs in Tangle-Predominant Alzheimer's Disease Mentor:
Michael L. Shelanski, M.D., Ph.D.
Columbia University Medical Center Summary: Neurofibrillary tangles (NFT), caused by clumping of toxic tau protein in the brain, are hallmarks of Alzheimer's disease (AD). The lack of a defined mechanism of NFT formation is impeding the development of new therapies. Dr. Santa-Maria Perez and colleagues will determine what is causing tau accumulation by looking for disease-causing variations in genes associated with AD, and by deciphering whether small gene “silencers,” called microRNAs, are the culprits for making one AD gene, called microtubule-associated protein tau (MAPT), go toxic. This research may reveal new targets of this type of Alzheimer's disease suitable for therapy. Program: Alzheimer's Disease  Sangram Sisodia, Ph.D.University of Chicago Title: Structure and Functional Analysis of Nicastrin Co-PI(s):
Shohei Koide, Ph.D.
University of Chicago Summary: Gamma-secretase is a complex of membrane proteins consisting of presenilin 1 or presenilin 2 (PS1 or PS2), APH-1, nicastrin (NCT) and PEN-2. It is now certain that PS serves as the catalytic center of the complex, but our understanding of the roles of the individual components in promoting gamma-secretase activity is still limited. We have chosen to examine NCT, a molecule proposed to serve as a receptor that facilitates engagement of the substrate with the catalytic site. The central aim of our study is to understand the structure and function of NCT with the notion that we will gain insights into the differential recognition of substrates, information that will be of immense interest in academic and pharmaceutical interests that are focused on the development of novel gamma secretase modulators as therapeutics for AD. Program: Alzheimer's Disease  Reisa Sperling, M.D.Brigham and Women's Hospital Title: Cholinergic Vulnerability in Amyloid-Positive Elderly Summary: This study will use a "scopolamine stress test" to test the hypothesis that older individuals harboring hidden amyloid pathology, as identified through brain imaging, are more vulnerable to the effects of the stress test on memory performance and functional MRI measures of memory network activity. Program: Alzheimer's Disease Peter M. Tessier, Ph.D.Rensselaer Polytechnic Institute Title: Structure of Abeta C-Terminal Domain in Toxic Oligomers Summary: The seminal event in Alzheimer's disease is the misfolding and clumping of a protein fragment into small particles that are highly toxic to brain cells. Why such peptide particles are toxic, while other particles composed of the same peptide are non-toxic, is one of the key unanswered questions in Alzheimer's disease research. We seek to explain the structural differences between toxic and non-toxic peptide particles with the long-term goal of guiding the rational design and development of new therapeutics to treat Alzheimer's disease. Program: Alzheimer's Disease Last Review: 04/29/13 |
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