A large analysis of brain imaging and clinical data from more than 17,000 older adults is revealing a more complex picture of Alzheimer’s disease risk across populations.
As new Alzheimer’s drugs increasingly target amyloid plaques in the brain, researchers are working to understand whether the biology behind the disease is the same for everyone. A new study suggests the answer may be more complicated than previously thought.
Analyzing brain imaging and clinical data from more than 17,000 participants across five major aging and Alzheimer’s studies, researchers at the USC Mark and Mary Stevens Neuroimaging and Informatics Institute (Stevens INI) found that Hispanic participants generally had lower amyloid levels than non-Hispanic white participants with similar cognitive status and genetic risk factors. The findings were published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Amyloid plaques are a key hallmark of Alzheimer’s disease, and APOE ε4 is the strongest common genetic risk factor for developing the late-onset form of the disorder. While both groups showed higher amyloid levels when carrying APOE ε4 or experiencing cognitive impairment, the association appeared weaker among Hispanic participants.
“APOE ε4 is a major Alzheimer’s disease genetic risk factor, but our results suggest its relationship to amyloid buildup may be more nuanced in Hispanic populations,” said Cally Xiao, PhD, the study’s lead author and a researcher at the Stevens INI. “This work is important because it may influence how we interpret risk, understand cognitive decline, and ultimately design or apply treatments across diverse communities.”
Leveraging Global Alzheimer’s Data
The project relied in part on the Global Alzheimer’s Association Interactive Network (GAAIN), a data sharing platform created at the Stevens INI with support from the Alzheimer’s Association. GAAIN enables scientists to find, explore, and connect large datasets from studies of Alzheimer’s disease, related dementias, and aging from around the world.
Through GAAIN, the researchers identified studies that reported amyloid PET scan results using the Centiloid scale, a standardized system that allows amyloid measurements to be compared across different imaging tracers, scanners, and research sites.
The team gathered data from five major research efforts: the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s study, the Alzheimer’s Disease Neuroimaging Initiative, the Health and Aging Brain Study–Health Disparities, the Imaging Dementia–Evidence for Amyloid Scanning study, and the Standardized Centralized Alzheimer’s and Related Dementias Neuroimaging initiative.
Combining these datasets allowed the researchers to identify trends that may have been difficult to detect within any individual study.
“This is exactly the kind of work GAAIN was built to enable,” said Arthur W. Toga, PhD, director of the Stevens INI and senior author of the study. “When researchers can identify compatible datasets, connect across studies, and conduct analyses at a scale that no one group could achieve independently, we gain a much clearer view of Alzheimer’s disease. That is especially important when we are trying to understand how disease biology may differ across populations that have historically been underrepresented in research.”
Comparing Amyloid Burden Across Populations
The analysis included 17,017 older adults, of whom 1,427 identified as Hispanic. Researchers used Centiloid scores to measure amyloid burden while accounting for factors such as age, sex, education, and cognitive performance.
Across the full study population, people with mild cognitive impairment or dementia tended to have higher amyloid levels than cognitively healthy participants. Carrying the APOE ε4 variant was also associated with greater amyloid burden in both Hispanic and non-Hispanic white participants.
Even so, Hispanic participants consistently showed lower average amyloid levels than non-Hispanic white participants across diagnostic categories. Among APOE ε4 carriers, Hispanic adults with either normal cognition or mild cognitive impairment also had lower amyloid levels than their non-Hispanic white counterparts.
The researchers also found that APOE ε4 had a weaker association with amyloid pathology among Hispanic participants. Non-Hispanic white carriers of APOE ε4 were more than four times as likely to show evidence of amyloid pathology, while Hispanic carriers were about two and a half times as likely.
“These findings do not mean that Hispanic adults are at lower risk for dementia,” Xiao said. “In fact, Hispanic populations face a higher overall burden of dementia. Instead, our results suggest that cognitive impairment in Hispanic older adults may not always be driven by amyloid in the same way, and that other biological, vascular, or social factors may also be important.”
Implications for Alzheimer’s Treatment and Research
The findings come as anti-amyloid therapies are becoming an increasingly important part of Alzheimer’s treatment. Because these drugs are designed to target amyloid plaques in the brain, understanding how amyloid burden relates to cognitive decline and genetic risk in different populations could have important implications for patient care.
The researchers emphasize that further studies are needed, including larger groups of Hispanic participants, more detailed information about ancestry and Hispanic origin, and long-term data tracking changes in amyloid levels and cognition.
They also note that vascular health and other medical conditions may help explain some of the observed differences, although those factors do not appear to account for the findings entirely.
“Alzheimer’s disease is complex, and the path to cognitive decline may not look identical for every population,” Toga said. “To move toward more precise and equitable care, we need research that reflects that complexity. Large-scale data resources such as GAAIN are helping make that possible.”
Reference: “Association of cognitive impairment and APOE ε4 with Centiloids in Hispanic and non-Hispanic White cohorts” by Cally Xiao, Tyler Ard, Ganna Blazhenets, Renaud La Joie, Ioannis Pappas, Arthur W. Toga, the Alzheimer’s Disease Neuroimaging Initiative, and the Health and Aging Brain Study (HABS-HD) Study Team, 11 June 2026, Alzheimer’s & Dementia.
DOI: 10.1002/alz.71586
Data used in the research were obtained through GAAIN, which is funded by the Alzheimer’s Association and powered by the Laboratory of Neuro Imaging at the USC Stevens Neuroimaging and Informatics Institute. The study was supported by the Global Alzheimer’s Association Interactive Network initiative of the Alzheimer’s Association, grant SG-20-678486-GAAIN2.
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