Researchers at the USC Mark and Mary Stevens Neuroimaging and Informatics Institute (Stevens INI) at the Keck School of Medicine of USC have found that a key Alzheimer’s disease risk factor may influence Hispanic older adults differently than non-Hispanic white adults. Analysing brain imaging and clinical data from more than 17,000 participants across five major ageing and Alzheimer’s disease studies, the team discovered that although greater amyloid buildup was linked to cognitive impairment and the APOE ε4 genetic variant in both groups, Hispanic participants generally had lower amyloid levels than non-Hispanic white participants with similar characteristics. The findings were published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Amyloid plaques are a hallmark biological feature of Alzheimer’s disease. At the same time, APOE ε4 is the strongest common genetic risk factor for late-onset Alzheimer’s and is typically associated with increased amyloid accumulation. However, the study suggests this relationship may not be equally strong across populations. “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 lead author Cally Xiao, PhD, a researcher at the Stevens INI. She noted that the findings could improve how researchers interpret risk, understand cognitive decline, and develop treatments for diverse communities.
The research was made possible through the Global Alzheimer’s Association Interactive Network (GAAIN), a data-sharing platform developed at the Stevens INI with support from the Alzheimer’s Association. GAAIN enabled the team to identify and combine compatible datasets using the Centiloid scale, a standardised measure of brain amyloid levels across different imaging methods. Data were drawn from five major studies, including the Alzheimer’s Disease Neuroimaging Initiative and the Health and Aging Brain Study–Health Disparities, allowing researchers to analyse patterns that would have been difficult to detect in any single study.
The researchers examined data from 17,017 older adults, including 1,427 Hispanic participants, while accounting for factors such as age, sex, education, and cognitive performance. As expected, individuals with mild cognitive impairment or dementia generally had higher amyloid levels than cognitively healthy participants, and APOE ε4 carriers in both ethnic groups showed greater amyloid burden. However, Hispanic participants consistently had lower average amyloid levels than non-Hispanic white participants across diagnosis groups. Among APOE ε4 carriers with normal cognition or mild impairment, Hispanic participants also had lower amyloid levels.
The team found that while APOE ε4 remained associated with amyloid pathology in both groups, its effect was weaker in Hispanic participants. Non-Hispanic white APOE ε4 carriers were more than four times as likely to show evidence of amyloid pathology, compared with about two and a half times among Hispanic carriers. Xiao emphasised that these findings do not suggest Hispanic adults face a lower risk of dementia. Instead, they indicate that cognitive decline in Hispanic older adults may not always be driven by amyloid to the same extent, with other biological, vascular, or social factors likely contributing to disease risk.
The findings have important implications as anti-amyloid therapies become increasingly central to Alzheimer’s treatment. Because these medications target amyloid plaques, understanding how amyloid accumulation varies across populations is essential for ensuring equitable and effective care. The authors stress that further research involving larger and more diverse Hispanic populations, more detailed ancestry information, and long-term follow-up is needed. Senior author Arthur W. Toga, PhD, said large-scale resources such as GAAIN are helping researchers better understand the complexity of Alzheimer’s disease and move towards more precise, inclusive approaches to diagnosis and treatment.
More information: Cally Xiao et al, Association of cognitive impairment and APOE ε4 with Centiloids in Hispanic and non-Hispanic White cohorts, Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. DOI: 10.1002/alz.71586
Journal information: Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association Provided by Keck School of Medicine of USC
