Find all causes of Alzheimer's disease and a cure

Stem cells long have been the mythical Excalibur of Alzheimer’s disease research—imbued with almost magical qualities that could allow us to conquer this nearly impossible disease. For decades, though, hope has outshone reality.  

The Opportunity  

This ambitious new project was funded by a generous group of individuals, foundations and trusts—without which exploring this new frontier would not be possible. 

The Power of Stem Cells

Stem cells are different from all other human tissue in three important, unique ways. First, they are unspecialized. Second, they can renew themselves by cell division. Third, they can be directed under certain conditions to become a wide variety of permanently specialized cells. In 1981, scientists discovered how to isolate embryonic stem cells from mouse embryos; in 1998, they devised how to grow human embryonic stem cells in a laboratory.  

The more recent breakthrough is the ability to genetically induce a specialized adult cell, such as a common skin cell, into reverting back to an unspecialized stem cell. Once generated, these pluripotent stem cells (iPS’s) are able subsequently to be directed to become a specialized cell—such as a neuron.  

Thus, an ordinary skin cell can now, in a lab, be converted into a neuron. From here, the hope is to create a new universe of Alzheimer’s nerve cells living outside the human brain in order to study and test new drugs much faster than researchers currently are able. To get there, the seven-member stem cell consortium, assembled by Sam Gandy, M.D., Ph.D., at Mount Sinai Medical Center, will have to first complete a number of precise tasks:

• ·         Generate iPS cells and neurons from the skin cells of Alzheimer’s patients. This already has been accomplished by Scott Noggle, Ph.D., of the New York Stem Cell Foundation and Kevin Eggan, Ph.D., of the Harvard Stem Cell Institute. Mark Tessier-Lavigne, Ph.D., president of The Rockefeller University, also has done important Cure Alzheimer’s Fund-funded work to determine the best method for obtaining these cells.
• ·         Perform molecular and biochemical analysis of new laboratory neurons. The newly converted Alzheimer’s neurons can be examined both in a laboratory dish and by transplanting them into the brains of host mice. Dr. Gandy already has discovered amyloid beta metabolism abnormalities in the Alzheimer’s neurons. Future studies will examine how the neurons respond to various stresses.
• ·         Profile the Alzheimer’s neurons. Drs. Noggle, Eggan and Gandy will establish a baseline molecular characterization of nerve cells from Alzheimer’s patients to determine the similarities and differences between those neurons and non-Alzheimer’s neurons.
• ·         Generate human neurons
  with known Alzheimer’s genes. Dr. Doo Yeon Kim, Ph.D., will establish various Alzheimer’s cell models designed to overexpress various known genetic mutations in order to enhance Alzheimer’s pathology.
• ·         Plant the new human neurons in mouse brains. Drs. Kim and Tanzi will establish a method to graft newly created neurons into mouse brains and analyze various disease markers in the months after cell injections. Tamir Ben-Hur, M.D., Ph.D., of Hadassah University Medical Center in Jerusalem will help choose which genetically manipulated mice are most likely to accept a stem cell transplant, and will guide the manipulation of these substances using small molecules and drugs in order to determine how best to keep stem cells alive.
• ·         Identify functional properties of human Alzheimer’s cells. Ben-Hur will conduct various tests on lab-created Alzheimer’s neurons inside and outside of mouse brains. He will gather new information on how Alzheimer’s neurons survive and connect in the brain environment.
• ·         Create a new choline acetyltransferase (ChAT) human pluripotent reporter cell line. Dr. Eggan will attempt to create a new cell line for studies into the in vitro generation of human cholinergic neurons.

Together the CAFSCC team will develop, study and maintain Alzheimer’s neurons that will be used to screen for new drugs. In keeping with Cure Alzheimer’s Fund’s principle of openness, this stem cell “bank” also will be made available to other researchers throughout the world. “We have great expectations for this project,” said Tanzi. “It could greatly accelerate the process of drug discovery.”