Indiana University Projects to Support Precision Medicine for Alzheimer’s

Researchers at Indiana University (IU) School of Medicine received a 5-year, $41 million grant from the National Institute on Aging (NIA) to fund a study investigating the pathology of Alzheimer’s disease and driving precision medicine approaches for the condition.

The study, called ‘Centrally-linked Longitudinal Peripheral Biomarkers of [Alzheimer’s Disease]’ (CLEAR-AD), is co-led by IU and Mayo Clinic in Florida and aims to combine single cell analysis of human brain tissue, longitudinal brain imaging, and blood-based biomarker research to help enable earlier and less-invasive diagnosis of Alzheimer’s.

“While we currently have very powerful and informative measures for Alzheimer’s diagnosis, most are slightly invasive and focused on amyloid plaques and tau tangles,” said Andrew Saykin, PsyD, director of the Indiana Alzheimer’s Disease Research Center and the IU Center for Neuroimaging who serves as a principal investigator on the study, in the press release.

“CLEAR-AD will use a systems biology approach to better understand those factors that drive these pathological hallmarks in the first place,” Saykin continued. “There has been great recent progress with the development of blood tests, but assessing multiple biological pathways earlier and noninvasively could make diagnosis more accessible and treatment plans more individually tailored for each patient.”

CLEAR-AD will include three related projects in these areas, data from which will be shared with the scientific community to support collaborative research.

The first will study brain tissue from the Mayo Clinic Study of Aging (MCSA) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI) using single cell and single nucleus sequencing. These analyses will help researchers understand variations in gene expression among brain cells from seven brain regions.

From there, research teams will create a database of molecular signatures connecting brain and blood for use in other studies.

The second project will investigate endophenotypes in relation to blood. Endophenotypes are measurable biological traits related to Alzheimer’s disease that can be evaluated using MRI and PET brain imaging, fluid biomarkers, and clinical tests, such as cognitive performance assessments.

Researchers will work to find associations between endophenotypes identified in this project and molecular signatures from brain cells in project one, which the press release indicates may drive insights into stage-specific disease evolution mechanisms and potential therapeutic targets.

The third project seeks to address knowledge gaps about how Alzheimer’s affects multi-ethnic populations. Statistics from the Centers for Disease Control and Prevention (CDC) indicate that Black and Latino adults are at a significantly higher risk of Alzheimer’s disease and related dementias (ADRD) than their White counterparts, and the disparities are projected to grow over time.

In addition to being more likely to develop Alzheimer’s, these populations are also less likely to be diagnosed because of various access and care barriers.

The third CLEAR-AD project will connect molecular signatures from project one and endophenotypes from project two with patterns observed among these groups using data from multiple Alzheimer’s Disease Research Centers (ADRCs).

“CLEAR-AD will allow us to connect what we see in peripheral blood and on imaging to what we see in brain tissue, which will be paramount in the opportunity to create the next generation of blood tests to diagnose individuals with Alzheimer’s disease even earlier when the disease is most treatable,” explained Kwangsik Nho, PhD, another principal investigator on the study who serves as associate professor of radiology and imaging sciences at IU School of Medicine.

This research is only of the Alzheimer's-related efforts being undertaken at IU.

Recently, IU Health and IU School of Medicine launched a new pilot program that aims to leverage artificial intelligence (AI)-based digital screening tools to drive early detection of cognitive impairment in the primary care setting.

In an interview with HealthITAnalytics last month, Jared Brosch, MD, a neurologist at IU Health and assistant professor of clinical neurology at IU School of Medicine, and Phyllis Ferrell, global head of external engagement for Alzheimer’s disease at Eli Lilly & Company and director of the DAC Healthcare System Preparedness initiative, discussed how the pilot can help support improved Alzheimer’s outcomes.