Researchers Focus on Building a Resilient Brain To Prevent Alzheimer’s Disease

A new research study at the University of Arizona Health Sciences will focus on identifying potential therapeutic targets and opportunities to prevent or delay the course of Alzheimer’s disease, which currently affects more than 6 million people in the United States. This number is rapidly increasing with the growing population of people age 65 or older, which is expected to outnumber those under 18 by 2035.

Late-onset Alzheimer’s disease, which accounts for more than 95% of all cases, can be caused by many factors, including intersecting genetic and environmental risks. The strongest genetic risk factor is ApoE4, a gene involved in the metabolism of fat in the body. ApoE4 has also been found to affect brain energy metabolism, but the underlying mechanisms are poorly understood.

“This research will help us understand highly complex mechanisms, at the cellular level, that alter brain energy supply and lipid homeostasis,” said Fei Yin, PhD, assistant director of translational neuroscience for the Center for Innovation in Brain Science and an assistant professor of pharmacology in the UArizona College of Medicine – Tucson.

The $1.1 million grant, Dr. Yin’s first from the National Institutes of Health, will advance research to understand the complexities underlying ApoE4-driven Alzheimer’s risks.

The study will continue Dr. Yin’s work that was published in the January 2021 issue of Cell Reports, which found that ApoE4 impairs the elimination of detrimental lipids from the brain. This disruption, coordinated by the nerve cells (neurons) and their supporter cells (astrocytes), consequently leads to energy deficit and malfunction of the brain.

“This grant provides us with the resources to elucidate the mechanistic basis towards novel Alzheimer’s disease therapeutics by reversing the disrupted lipid metabolism in brain, which is particularly significant for the most vulnerable ApoE4 gene carriers,” Dr. Yin said.

Dr. Yin and his team expect to fill the knowledge gaps in how cell types with distinctive metabolic characteristics jointly maintain the metabolic landscape of the brain. His research will have a translational impact, shedding light on selective cell vulnerability in Alzheimer’s disease development.

"Dr. Yin’s work has many implications for understanding and developing therapeutic interventions for late-onset Alzheimer’s disease," said Center for Innovation in Brain Science Director Roberta Diaz Brinton, PhD. "The bioenergetic changes that occur with the aging brain are at the heart of this important research.”   

This study is supported by the National Institutes on Aging, a division of the National Institutes of Health (RF1AG069175-01A1).