UCI MIND investigators Mathew Blurton-Jones, PhD, Assistant Professor of Neurobiology & Behavior, Wayne Poon, PhD, Director of UCI MIND Tissue Repository, and Edsel Abud, MD/PhD student, have created a method to generate brain cells called microglia using human skin cells. Here, they discuss their findings and what it means for Alzheimer’s disease research in an interview with Chelsea Cox, Associate Director of Education:
What is microglia and what role does it play in Alzheimer’s disease?
Poon: Microglia are the immune cells of the brain. They play a big role in the inflammation of the brain that occurs in Alzheimer’s disease.
How can induced pluripotent stem cells be used to better understand the role of microglia in Alzheimer’s disease?
Blurton-Jones: Induced pluripotent stem (iPS) cells, which can be derived from human blood and skin, can be made into every cell type in the human body, including microglia. This allows us to study the role of microglia in Alzheimer’s disease safely and efficiently in a dish.
You recently published a paper in Neuron on how to create human microglia-like cells from iPS cells. Can you summarize what you did, what you found, and why it is important?
Abud: We developed a method to make microglia from iPS cells. We then used these cells to study how microglia are influenced by toxic proteins like amyloid beta and tau, which are found in Alzheimer’s disease. We found that many of the genes associated with modifying Alzheimer’s disease risk are altered in microglia when exposed to these toxic proteins. This knowledge allows us to design ways to study potential therapies for Alzheimer’s disease, targeting what we discovered.
How will this new study help Alzheimer’s disease researchers worldwide?
Blurton-Jones: In the past six months, a couple of protocols to make microglia cells have been proposed, but what is unique about ours is that it allows researchers to make microglia in large numbers and study their function and interactions with neurons in 3D brain models. Scientists can then use these cells to look at drugs that actually modify or alter function of the microglia and potentially prevent or reverse the detrimental effects of the amyloid and tau on microglial function.
Do you think your findings will help move the field closer to improved treatments and a cure for Alzheimer’s disease? How?
Poon: Absolutely. Prior to the development of this protocol, it was really hard to study how these cells are functioning in the brain. The only way to study human microglia was to isolate the cells from human brain tissue during neurosurgery. Our protocol enables the study of human microglial function in a dish, where we can screen drugs and facilitate new discoveries, not only in Alzheimer’s disease but also in other neurodegenerative diseases like Parkinson’s disease, Huntington’s disease and frontotemporal dementia, which are also associated with inflammation and microglia.
Did you learn anything else from this study that everyday people who have a family member with Alzheimer’s disease or are concerned about it themselves might like to know?
Abud: We have to be cautionary about what these results mean for people affected by Alzheimer’s disease and their family members. What I would tell my grandmother, who is affected by Alzheimer’s disease, and other people in my family is that there is a dramatic change in how we are studying Alzheimer’s disease. We now know that the immune system really plays a role in modifying this disease, and we hope these findings open up new and specific targets for treatment. Even though there are promising immunotherapies in development as candidate treatments for Alzheimer’s disease, we as a field will continue to strive for new and more effective therapies. I hope that the development of these iPS-microglia will help with that progress. So I think there’s a lot of hope, a lot more tangible hope now than there was before.