News Release

Study identifies biomarkers that could guide precision medicine therapies for Alzheimer's disease

logo for the University of Arizona Health Sciences April 28, 2022 study identifies biomarkers that could guide precision medicine therapies for Alzheimer's disease novel findings from research at the Center for Innovation in Brain Science indicate the APO

Peer-Reviewed Publication

University of Arizona Health Sciences

TUCSON, Arizona — A University of Arizona Health Sciences study found that a specific genotype of the APOE gene, better known as the Alzheimer’s gene, is able to significantly influence metabolic changes and override sex-specific differences between men and women with Alzheimer’s disease.

The discovery may provide critical insights for personalized medicine related to late-onset Alzheimer’s disease, a complex neurodegenerative disease characterized by multiple progressive stages including cognitive decline. 

“One of the most interesting findings of our study is the identification of key drivers of metabolic pathways that discriminate between Alzheimer’s disease and cognitively normal individuals when patient groups were separated by sex and APOE genotype,” said Rui Chang, PhD, a member of the University of Arizona Health Sciences Center for Innovation in Brain Science and lead author of the study. “These patient-specific metabolic targets will shed light on the discovery of precision therapeutics for Alzheimer’s patients, which has not been done in previous studies.” 

The paper, “Predictive metabolic networks reveal sex and APOE genotype-specific metabolic signatures and drivers for precision medicine in Alzheimer’s Disease,” was published today in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association.

The APOE gene is involved in making a protein that helps carry cholesterol and other types of fat in the bloodstream. There are several genotypes, or variations, of APOE based on the specific gene variants an individual inherits. The APOEe4 genotype has been identified as a risk factor for Alzheimer’s disease.

Dr. Chang and the research team integrated a metabolic network model with advanced machine learning approaches to perform a computational analysis on 1,517 serum samples provided by the Alzheimer’s Disease Neuroimaging Initiative.

First, they identified common metabolic signatures of late-onset Alzheimer’s disease. Next, they separated the network into clusters by sex to identify sex-specific metabolic changes and by genotype to identify other metabolic signatures influenced by the APOEe4 genotype.

Finally, they stratified patients by intersection of sex and APOEe4 status together and found that the APOEe4 genotype was able to significantly influence metabolic changes while overriding sex-specific differences in males and females.

Additionally, they identified serum-based metabolic biomarker panels that are predictive of disease state and associated with clinical cognitive function for each of the eight patient subgroups stratified by sex and/or APOEe4 status.

These novel patient-specific metabolic panels identify key metabolic drivers of late-onset Alzheimer’s disease that could be evaluated as therapeutic targets. The findings have the potential to greatly accelerate drug development for Alzheimer’s disease while providing outcome measures for clinical trials.

"Dr. Chang’s research provides an initial but critical step toward the development of personalized and precision medicine for Alzheimer’s disease,” said Roberta Diaz Brinton, PhD, Regents Professor of Pharmacology and director of the Center for Innovation in Brain Science. “This study provides an operational strategy to achieve that goal by integrating clinical cognitive assessments, metabolic profiling and a computational network model to identify targeted therapeutics for patients.” 

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About the University of Arizona Health Sciences
Located on campuses in Tucson, Phoenix and Gilbert, Ariz., the University of Arizona Health Sciences is one of the top-ranked academic medical centers in the southwestern United States. UArizona Health Sciences includes the College of Medicine – Phoenix, College of Medicine – Tucson, College of Nursing, Mel and Enid Zuckerman College of Public Health, R. Ken Coit College of Pharmacy, and Health Sciences Global and Online. In addition, 15 UArizona Health Sciences centers and programs focus on cancer, neurodegenerative diseases, pain and addiction, and respiratory diseases; biomedical informatics, health technology innovation and simulation training; and health disparities, precision health care and treatments, and pandemic preparedness. A leader in next-generation education, research, clinical care and public outreach, UArizona Health Sciences employs nearly 5,000 people, has approximately 4,000 students and 900 faculty members, and garners more than $220 million in research grants and contracts annually. For more information: (Follow us: Facebook | Twitter | YouTube | LinkedIn | Instagram).

About the Center for Innovation in Brain Science
The Center for Innovation in Brain Science (CIBS) at the University of Arizona is addressing the challenge that, in the 21st century, there is not a single cure for a neurodegenerative disease. The CIBS team is focused on four age-associated neurodegenerative diseases: Alzheimer’s, Parkinson’s, Multiple Sclerosis and ALS (or Lou Gehrig’s disease). With expertise spanning discovery, translational, regulatory and clinical science, CIBS is shifting the research paradigm as one of the nation’s leading research centers, pioneering patient-inspired, data-driven approaches to find cures for Alzheimer’s and other neurodegenerative diseases. The CIBS mission is to create innovations in brain science of the future for those who need a cure today. Find out more about how CIBS is achieving the vision of vibrant brains that last a lifetime. For more information: (Follow us: Facebook | Twitter).

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