Stem cells are the generic “raw materials” an adult human body transforms and uses to repair and replenish its various kinds of tissues. Because these cells are undifferentiated, they can be treated with a defined cocktail of factors in a set sequence to cause maturation of cells into discrete cell types. With a new tool called induced pluripotent stem cells (iPS cells), it now is possible to take skin cells from adults and return them to this immature state. By redirecting skin cells from Alzheimer’s patients and turning them into nerve cells, we are able to study adult Alzheimer’s neurons (nerve cells) in the lab. These Alzheimer’s neurons can be studied either in a dish or by transplanting them into the brains of host mice.
The Cure Alzheimer’s Fund Stem Cell Consortium team has developed, studied and maintained Alzheimer’s neurons that will be used to screen for new drugs. This “Stem Cell Bank” is available for use by these and other researchers around the world to accelerate drug screening. The first targets for such screening are drugs that already have been proven safe in humans. Other targets will include compounds developed specifically to interrupt Alzheimer’s pathology. Most excitingly, new drugs will be based on new clues that will arise only from the study of these human Alzheimer’s neurons.
An important outcome of our stem cell research was the development of “Alzheimer’s in a Dish,” reported in The New York Times as a ‘giant step forward’ for the field. Using non-embryonic stem cells, Doo Kim and Rudy Tanzi successfully grew Alzheimer’s neurons in a Petri dish and directly observed the development of both amyloid and tau pathology. This near-ideal lab model of Alzheimer’s will “dramatically accelerate drug testing,” according to Tanzi. The breakthrough also served to confirm the long-debated amyloid hypothesis, by allowing researchers to see precisely how amyloid stimulates the creation of tau “tangles.”
Although the initial Alzheimer’s in a Dish model was a breakthrough, Cure Alzheimer’s Fund researchers have not rested on their laurels. New projects are expanding the scope and utility of the model by adding inflammation markers and mimicking the role of the blood-brain barrier to make an even more accurate laboratory replica of the human neuronal environment.
Stem Cell Approach to Investigating the Phenomenon of Brain Insulin Resistance
What is the evidence that “brain insulin resistance” is a consistent feature of Alzheimer’s disease? The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) convened a summit in the summer of 2015 wherein the major question for new research focuses on establishing molecular and physiological criteria for “brain insulin resistance.” Several investigators have proposed that brain insulin resistance is a feature of human AD.
iPS-derived and trans-differentiated human neurons as models to study Alzheimer’s disease
Recent groundbreaking work in stem cell biology has made it possible to reprogram non-neuronal cells obtained from Alzheimer’s diseased patients into neurons. For the first time, the research community has the means to study diseased human neurons from Alzheimer’s patients. These models have already yielded novel insights into the disease.