Published on: July 16, 2012
by PR Newswire for Wall Street Journal:
Researchers at the Alzheimer’s Association International Conference® 2012 (AAIC® 2012) today reported the creation of a new model of Alzheimer’s derived from the skin cells of people with the disease that were reprogramed into Alzheimer’s brain cells.
This new Alzheimer’s model may prove to be more accurate than current mouse models of the disease and therefore can be used (a) to generate important new insights into the biology of Alzheimer’s and related disorders and (b) for early stage testing of new therapies.
“Current animal models of Alzheimer’s are highly engineered to express elements of the disease, and, while valuable for research, incompletely represent how the disease forms and progresses in people,” said William Thies, PhD, Alzheimer’s Association® Chief Medical and Scientific Officer. “In order to develop better therapies and eventually prevent Alzheimer’s, we need better, more accurate animal and cellular models of the disease. This newly reported research is a significant step forward in that direction.”
Most of the current Alzheimer’s mouse models incorporate genetic changes found in familial young-onset forms of Alzheimer’s. Although these mice have taught us about many valuable aspects of the disease, the hallmark amyloid plaques found in the brains of people with Alzheimer’s do not form in the same way as in the brains of mice expressing mutant forms of the most common young-onset Alzheimer’s gene, and significant brain cell death does not occur. New approaches are needed.
Andrew Sproul, PhD, a postdoctoral associate, and colleagues working at The New York Stem Cell Foundation (NYSCF) in the laboratory of Scott Noggle, PhD, the NYSCF-Charles Evans Senior Research Fellow for Alzheimer’s Disease, pursued an induced pluripotent stem cell (iPSC) approach to model Alzheimer’s, and reported their results for the first time today at AAIC 2012. This involves taking cells from people with the disease and their unaffected family members, typically skin cells, and reprogramming them by adding genetic factors. The resulting iPSCs can be used to model Alzheimer’s in a dish.
“One advantage of this technology is that we get a near infinite supply of disease and control patient stem cells,” Sproul said. “Another is that we can then turn the iPSCs into any tissue in the body. This allows us to investigate the role of various cells in Alzheimer’s disease progression by manipulating the iPSCs to form different types of brain cells (forebrain nerve cells, neural stem cells, glial cells) that we and others believe are involved in Alzheimer’s.”
The researchers generated iPSCs from a total of 12 people with Alzheimer’s and healthy controls from two young-onset, genetic Alzheimer’s families. The iPSC lines have been quality-controlled, including ensuring pluripotency, which is the ability to make all kinds of cells from the endoderm (interior stomach lining, gastrointestinal tract, lungs), mesoderm (muscle, bone, blood, urogenital), or ectoderm (skin and nervous system).
“We have made both the control and Alzheimer’s iPSCs into brain cells and have demonstrated that they are electrically active. These new brain cells include forebrain cholinergic neurons, which are particularly vulnerable in Alzheimer’s disease,” Sproul said.
“We have also begun to use the iPSC-derived neurons and neural stem cells to compare differences in cellular function between people with Alzheimer’s and their unaffected relatives. For example, we, in conjunction with Dr. Sam Gandy’s group at Mount Sinai School of Medicine, have demonstrated that Alzheimer’s neurons produce more of the toxic form of beta amyloid, the protein fragment that makes up amyloid plaques, though this aspect of the research is preliminary,” Sproul added.
The research reported at AAIC 2012 focuses on people with presenilin-1 (PSEN1) mutations, which are responsible for the most common form of rare, inherited, young-onset Alzheimer’s (estimated to be less than two percent of total cases). According to Sproul, this work may provide a platform to screen new drugs that could alleviate defects caused by the faulty gene.
However, because the overwhelming majority of people with Alzheimer’s have the late onset “sporadic” form of the disease, the scientists say they plan to expand their research to include large-scale production of iPSCs from people with different types of Alzheimer’s.
“We have begun to extend this work by collaborating with four different institutions in New York City – the Mount Sinai School of Medicine, Columbia University, New York University, and Rockefeller University. Over the next few years, we expect to provide substantial insight into Alzheimer’s and valuable tools to help create the next generation of therapeutics,” Sproul said.
Picture Source: Science Daily
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