2021 Alzheimer's Association Research Grant (AARG)

Multidimensional Measurement in High Field NMR Capturing Neurodevelopment

How to better understand brain changes observed in Alzheimer’s using brain-like-structures engineered in the laboratory?

Rita Schmidt, Ph.D.
Weizmann Institute of Science
Rehovot, Israel

Background

The proteins beta-amyloid and tau accumulates to form plaques and tangles respectively, the two main hallmark brain changes observed in Alzheimer’s. Though studies indicate that plaques and tangles may hinder brain cell function and may be associated with cell death, the biological mechanisms underlying these brain changes is yet unclear. One reason for this uncertainty has been that the systems used to generate and study plaques and tangles in the laboratory do not necessarily simulate human nerve cell abnormalities in the living brain accurately.

Scientists have developed novel, three-dimensional brain-like structures called cerebral organoids that may more accurately represent the human brain. These structures are created in the laboratory from induced pluripotent stem cells (iPSCs), which are stem cells engineered from adult human skin cells and then “reprogrammed” into brain cells. When grown in a laboratory dish under the right conditions, a group of brain cells can mimic the structure and function of the brain tissue.
 
Brain organoids could prove to be useful in learning more about human brain biology and the brain changes associated with Alzheimer’s and other brain diseases. However, current methods of monitoring and assessing brain organoids may be invasive, which can harm the living cells. Using noninvasive methods could allow scientists to study development of brain cells over time in brain organoids and gain insights into the development and progression of brain diseases.

Research Plan

Dr. Rita Schmidt and colleagues will design and develop a non-invasive approach by combining two types of brain scans, magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) to study the various stages of development of nerve cells (brain cells) in brain organoids. The researchers will then study the biochemical and physical changes over time in cognitively unimpaired brain organoid tissue. Dr. Schmidt’s team will then compare them to changes in brain organoids made from cells from individuals with Alzheimer’s to better understand brain changes observed in Alzheimer’s.

Impact

The study results could give rise to a non-invasive approach to help understand the biology of brain cell development over time in a laboratory dish as well as brain changes observed in Alzheimer’s. If successful, this tool could be used by researchers in the Alzheimer’s and dementia research space.