Case Western Reserve Awarded $3.3M NIH Grant to Investigate Brain Proteins in Alzheimer’s Disease

In a significant step forward for Alzheimer’s disease research, Case Western Reserve University has secured a four-year, $3.3 million grant from the National Institutes of Health (NIH). The funding will support a study examining whether specific brain proteins, known as Eph receptors, play a role in the development of Alzheimer’s disease, a progressive brain disorder that affects millions of Americans. Researchers aim to uncover whether these proteins are involved in the breakdown of the brain’s protective barrier, potentially contributing to the onset of Alzheimer’s.

Alzheimer’s disease, which affects nearly 7 million people in the U.S. aged 65 and older, leads to the gradual destruction of memory and cognitive functions. It is a leading cause of death, surpassing breast and prostate cancer fatalities combined. Prior studies suggest that the disease may begin when the brain's blood-brain barrier (BBB) weakens, allowing harmful substances to enter and damage brain cells. However, much remains unknown about the precise mechanisms involved.

The research funded by this NIH grant will focus on the role of Eph receptors in the blood-brain barrier's disintegration. Eph receptors are proteins that mediate cell-to-cell interactions and were initially studied for their involvement in brain development and cancer. Matthias Buck, PhD, a professor of physiology and biophysics at Case Western Reserve, has spent 15 years studying these proteins. His new research aims to determine whether Eph receptors contribute to the weakening of the BBB, a key factor in the early stages of Alzheimer's and other brain-related conditions, such as stroke.

What makes this project especially noteworthy is its interdisciplinary approach. Buck's team is collaborating with researchers from Texas Tech University, the University of Tennessee, and Memorial Sloan Kettering Cancer Center. This team will use advanced imaging, computational techniques, and crystallography to investigate how Eph receptors behave in living cells and determine their structure. These insights could unlock new therapeutic targets for Alzheimer’s treatment.

The significance of this research lies in its potential to address a major global health challenge. If the study confirms that Eph receptors are critical to the integrity of the blood-brain barrier, it could lead to the development of therapies that prevent or slow the progression of Alzheimer’s disease. For millions of people affected by this devastating condition, such breakthroughs could offer hope for improved treatment options in the future.

This collaborative effort underscores the complexity of Alzheimer’s and the need for innovative, multi-disciplinary approaches. As Buck points out, “We anticipate this research will result in discoveries that will one day make it possible to treat an illness that impacts millions of people worldwide.”