17,000 Brain Scans Reveal Unexpected Ethnic Differences in Alzheimer’s Disease Biology

A large-scale analysis of brain imaging and clinical data from more than 17,000 older adults has revealed significant differences in Alzheimer’s disease biology across ethnic groups, highlighting the need for a more tailored approach to research and treatment. The findings come as new therapies targeting amyloid plaques become increasingly important in the management of Alzheimer’s disease.

Study Suggests More Complex Alzheimer’s Risk Patterns

Researchers at the USC Mark and Mary Stevens Neuroimaging and Informatics Institute examined data from five major ageing and Alzheimer’s studies and found that Hispanic participants generally had lower levels of amyloid plaques than non-Hispanic white participants with similar cognitive conditions and genetic risk factors.

The study, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, raises important questions about whether the biological processes underlying Alzheimer’s disease are consistent across different populations.

Amyloid plaques are one of the defining features of Alzheimer’s disease, while the APOE ε4 gene variant is widely recognised as the strongest common genetic risk factor for late-onset Alzheimer’s.

Although carrying the APOE ε4 variant and experiencing cognitive impairment were linked to higher amyloid levels in both groups, researchers found that the relationship was less pronounced 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, the study’s lead author and a researcher at the Stevens Institute.

“This work is important because it may influence how we interpret risk, understand cognitive decline, and ultimately design or apply treatments across diverse communities.”

Global Data Platform Enabled Large-Scale Analysis

The research relied heavily on the Global Alzheimer’s Association Interactive Network (GAAIN), a data-sharing platform developed by the Stevens Institute with support from the Alzheimer’s Association.

GAAIN allows scientists to identify, access and compare datasets from Alzheimer’s disease, dementia and ageing studies conducted around the world.

Using the platform, researchers identified studies that reported amyloid PET scan results using the Centiloid scale, a standardised measurement system that enables amyloid levels to be compared across different imaging methods, scanners and research sites.

The team combined data from five major initiatives:

• Anti-Amyloid Treatment in Asymptomatic Alzheimer’s
• Alzheimer’s Disease Neuroimaging Initiative
• Health and Aging Brain Study–Health Disparities
• Imaging Dementia–Evidence for Amyloid Scanning
• Standardized Centralized Alzheimer’s and Related Dementias Neuroimaging initiative

By bringing together multiple datasets, researchers were able to identify trends that may not have been visible within any single study.

“This is exactly the kind of work GAAIN was built to enable,” said Arthur W. Toga, director of the Stevens Institute 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.”

Lower Amyloid Levels Observed Among Hispanic Participants

The study analysed data from 17,017 older adults, including 1,427 participants who identified as Hispanic.

Researchers measured amyloid burden using Centiloid scores while accounting for factors such as age, sex, educational attainment and cognitive performance.

Across the full study population, people with mild cognitive impairment or dementia generally exhibited higher amyloid levels than cognitively healthy participants. Carrying the APOE ε4 variant was also associated with increased amyloid burden in both Hispanic and non-Hispanic white participants.

However, Hispanic participants consistently displayed lower average amyloid levels than non-Hispanic white participants across all 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.

Researchers further found that APOE ε4 had a weaker association with amyloid pathology among Hispanic participants. Non-Hispanic white carriers of the variant were more than four times as likely to show evidence of amyloid pathology, whereas Hispanic carriers were around 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 Future Alzheimer’s Treatments

The findings arrive as anti-amyloid therapies become an increasingly significant part of Alzheimer’s treatment strategies.

Because these medicines are specifically designed to target amyloid plaques in the brain, understanding how amyloid burden relates to cognitive decline and genetic risk across different populations could play an important role in patient assessment and treatment planning.

Researchers stressed that additional studies are needed, including larger Hispanic participant groups, more detailed information about ancestry and ethnic background, and long-term monitoring of amyloid levels and cognitive changes.

They also noted that vascular health and other medical conditions may contribute to the observed differences, although these factors do not appear to fully explain the results.

Towards More Personalised Dementia Care

The study underscores the growing recognition that Alzheimer’s disease may not follow the same biological pathway in every population.

“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.”

The findings provide fresh insight into the diversity of Alzheimer’s disease and suggest that future research, diagnosis and treatment approaches may need to account more carefully for differences between populations to ensure effective and equitable care.