The IU Impact: By combining pioneering methods in biosciences and biocomputing, we're gaining new ground in the fight to end Alzheimer's disease.
Feng Guo, right, positions an organoid slide as Ph.D. student Chunhui Tian prepares to review the image under a microscope at the IU Luddy School in Bloomington. Photo by Chris Meyer, Indiana University
Using little more than a few drops of blood, Indiana University scientists are applying advanced medical and engineering know-how to create simplified models of the brain for studying Alzheimer's disease.
Along with other dementias, the devastating illness currently impacts 7.2 million Americans, including 1 in 10 Hoosiers over age 65.
The work - spread across IU labs in Bloomington, Indianapolis and Terre Haute - is made possible by brain organoids, which are basic cellular clusters that mimic the structures of the human brain. Discovered about 10 years ago, these groundbreaking tools are offering scientists insights never previously seen into the function of the human brain.
When grown from the blood sample from an Alzheimer's patient, brain organoids can also provide a powerful way to study the genetics behind the disease. IU's brain organoids are grown from samples collected through the leading-class research happening at the IU School of Medicine, the country's largest medical school.
A growing crisis
The leader of these efforts at IU is Jason Meyer, an IU School of Medicine professor and director of a $16.5 million MPS-AD center established to study Alzheimer's disease using brain organoids, one of only two centers of its kind in the U.S.
"New treatments will have a huge impact on the day-to-day lives of people living with Alzheimer's or taking care of someone with Alzheimer's," said Meyer, whose great-grandmother had the disease. "This is a condition that not only affects the person with it over many years but also their families and caregivers."
Unlike other conditions whose rates are declining, such as heart attacks and stroke, Alzheimer's is on the rise and is now the sixth leading cause of death in adults over 65 in the United States.
Building on IU's strengths
The research leverages the university's deep expertise on Alzheimer's disease that has attracted global health leaders such as Bill Gates to its Indianapolis campus and major investments from world-class business partners, such as international pharmaceutical manufacturer Eli Lilly and Company.
Jason Meyer reviews samples under a microscope in his lab. Photo by Liz Kaye, Indiana UniversityThese efforts include other centers focused on understanding the biological pathways of Alzheimer's disease; improving model systems for early onset Alzheimer's; and identifying new Alzheimer's drug targets - the last of which has already discovered several promising compounds. All of these programs are supported by tens of millions of dollars in research funding and other investments.
Indiana University also houses the country's top facility for storing biological samples from patients with Alzheimer's. The site - where samples are stored at ultra-low temperatures and accessed through a robotic retrieval system - is the source of blood samples used to grow brain organoids at IU. It will also act as a clearinghouse for other researchers who want to study Alzheimer's disease with brain organoids grown at the university.
Brain science meets computer science
In addition to partners at the IU School of Medicine, a team led by Feng Guo at the IU Luddy School of Informatics, Computing and Engineering at IU Bloomington is applying its bioengineering skills to the challenging task of growing simplified brain structures. The collaboration underscores how IU approaches engineering as an interdisciplinary pursuit to improve human lives.
Coaxing cells to grow into brain organoids is sensitive work; tiny changes in the process can create big differences in the results. Errors in the process could even grow the wrong cell types, such as retinal organoids. Fortunately, Guo's lab has pioneered new methods to standardize organoid growth with automated, AI-powered microfluidic systems and microscopically small structures that guide their development.
Chunhui Tian, left, assists as postdoctorial fellow Hongwei Cai removes a rack of brain organoids from a large cryogenic storage tank in Guo Feng's lab. Photo by Chris Meyer, Indiana University
He is also applying expertise in another research area - the emergent field of biocomputing - to the fight against Alzheimer's.
This work involves connecting multiple brain organoids together, then interpreting how this system processes information. By examining the output of organoids created from healthy blood samples versus individuals with Alzheimer's, Guo's team can spot differences that could shed light on why people with the disease struggle with memory and pattern recognition.
"Brain organoids can provide real insights into differences in how the brain processes information, which research indicates is impaired in individuals with Alzheimer's disease," Guo said. "Our early results suggest that healthy organoids are better at pattern separation than Alzheimer's disease organoids."
The system also offers an innovative way to explore potential new drug treatments for Alzheimer's disease. If a chemical compound causes an Alzheimer's organoid to process signals more like a healthy one, it's worth deeper investigation.
Broadening research horizons
In addition to collaborating on MPS-AD, Guo and Meyer are among the researchers whose work is being bolstered by IU LAB, IU's incubator for bioscience research in partnership with industry.
Other researchers across the university are also leveraging Guo's brain organoid growth technology to find answers to other neurological disorders. One scientist at IU's Gill Institute for Neuroscience in Bloomington, also supported by IU LAB, is using organoids to advance the treatment of drug addiction.
Other scientists contributing to MPS-AD will use organoids for testing new drug compounds, identifying chemical changes in brain organoids that suggest the presence of Alzheimer's disease, and exploring how Alzheimer's disease affects other aspects of the brain, such as its effect on the brain's protective mechanisms.
The work will open new frontiers in Alzheimer's and other neurological research in the U.S. and around the world.
"We're engineering organoids that other labs can request and use, ready to go for experiments," Meyer said. "By generating fully functional organoids for the research community, IU's work will speed the scientific process and get us all closer to new solutions to this disease."
