Large global study examines Alzheimer’s blood biomarker across racial and ethnic groups

A large global study provides new evidence supporting the use of blood biomarkers in an Alzheimer’s clinical trial to screen for elevated brain amyloid levels among potential participants who are cognitively unimpaired. The findings, funded in part by the National Institutes of Health and just published in JAMA Neurology, show that the relationship between blood biomarker and brain amyloid was largely similar across racial groups. 

The study also revealed that levels of the biomarker were generally lower among Asian and Black participants compared with White participants, and Hispanic participants compared with non-Hispanic participants. These differences raise questions about the factors that influence blood biomarker levels and how they relate to dementia risk across populations.

Treatments such as lecanemab can slow cognitive decline in people with early symptomatic Alzheimer’s disease by targeting amyloid buildup in the brain. Clinical trials are now testing whether these drugs can delay cognitive decline in cognitively unimpaired individuals with elevated amyloid if taken before symptoms begin.

To help identify participants for these trials, researchers use a blood test that measures the proportion of a protein fragment carrying a specific Alzheimer’s-related modification, known as %p-tau217. The blood test helps identify individuals who are more likely to have elevated brain amyloid, which is then confirmed in the study with a positron emission tomography (PET) scan.

Because people from some populations have been historically underrepresented in these trials, researchers have sought to better understand how blood biomarkers related to brain amyloid across different groups.

“We found that %p-tau217 levels were lower in populations that have historically been underrepresented in clinical trials. Importantly, however, the relationship between the biomarker and brain amyloid was generally consistent across racial groups,” said Doris P. Molina-Henry, PhD, the study’s corresponding author and associate professor of research neurology with the Epstein Family Alzheimer’s Therapeutic Research Institute at the Keck School of Medicine of USC. “This supports the use of blood-based biomarkers as an initial screening tool for elevated amyloid in a preclinical Alzheimer’s disease trial.”

Linking %p-tau217 to genetic risk

The study included data from 15,612 adults, ages 55 to 80, collected at 106 research sites across Asia, Australia, Europe and North America. Participants were cognitively unimpaired and undergoing screening for the AHEAD 3-45 trials, which are testing lecanemab in people with certain levels of amyloid in the brain but no symptoms of Alzheimer’s disease. Participants underwent blood-based screening before eligible individuals proceeded to additional assessments, including PET scans.

Although %p-tau217 levels differed across racial and ethnic groups, the marker showed similar relationships with Alzheimer’s-related measures across racial groups. Across the groups studied, higher %p-tau217 levels were consistently associated with higher levels of brain amyloid measured on PET scans.

The study also found that carriers of the APOE ε4 variant, a major genetic risk factor for Alzheimer’s, generally had higher levels of %p-tau217 than adults without the variant—a pattern that largely held across racial and ethnic groups.

“These findings reinforce the relationship between APOE ε4 and Alzheimer’s-related blood biomarkers, while showing that the strength of this relationship can vary across populations,” Molina-Henry said.

Other causes of dementia

The findings also raise broader questions about dementia risk. Although Asian, Black and Hispanic participants had lower levels of the Alzheimer’s-related blood biomarker, prior research reports that Black and Hispanic groups have historically faced a higher overall risk of developing dementia.

“These findings remind us that dementia risk is complex and may involve multiple contributing factors beyond Alzheimer’s-related changes measured by this blood test or a PET scan,” Molina-Henry said. “Other processes in the brain may also play a role—and that warrants further study.”

The Alzheimer's Plasma Extension Study, or APEX, is following individuals who underwent AHEAD 3-45 screening but did not meet the amyloid eligibility criteria for the trials. By continuing to collect blood tests, PET scans and measures of cognition, the study will help researchers understand how these trajectories change over time in this group.

“Following these individuals over time will help us understand how Alzheimer’s-related biomarkers change and how those changes relate to brain amyloid and cognition,” Molina-Henry said.

About this research

In addition to Molina-Henry, the study’s other authors are Andy Liu, Oliver Langford, Rema Raman, Robert A. Rissman and Paul Aisen from the Epstein Family Alzheimer’s Therapeutic Research Institute, Keck School of Medicine of USC, University of Southern California; Keith Johnson and Reisa A. Sperling from Massachusetts General Hospital, Harvard Medical School; Dina Dass from Columbia University Irving Medical Center; Emily Clark from the University of Rochester School of Medicine and Dentistry; Gregory S. Day from Mayo Clinic Jacksonville; Hamid R. Okhravi from Eastern Virginia Medical School at Old Dominion University; Pallavi Joshi from Banner Health, Phoenix, Arizona; Paulette Cazares from Sharp HealthCare, San Diego, California; Raymond Scott Turner from Georgetown University; Joel B. Braunstein, Philip Verghese, Venky Venkatesh and Tim West from C2N Diagnostics, St. Louis, Missouri; Shobha Dhadda and Michael Irizarry from Eisai, Nutley, New Jersey; and Joshua D. Grill from the University of California, Irvine.

The AHEAD Study is a public-private partnership between the Alzheimer’s Clinical Trial Consortium [NIA U24 AG057437], the National Institutes of Health [R01 AG095009; R01 AG061848)] and Eisai, with additional support provided by the Alzheimer’s Association, the GHR Foundation and philanthropic organizations.