A team of researchers at the USC Mark and Mary Stevens Neuroimaging and Informatics Institute ( Stevens INI ) at the Keck School of Medicine of USC has identified important differences in how early Alzheimer's disease-related brain changes appear across racial and ethnic groups, underscoring the need for more inclusive approaches to studying and diagnosing the disease. Their findings are now available in Alzheimer's & Dementia: The Journal of the Alzheimer's Association .
In a large, racially and ethnically diverse study of older adults without dementia, researchers found that Black and Hispanic participants showed higher levels of tau, a protein linked to Alzheimer's, in key memory-related regions of the brain compared to non-Hispanic white participants, even before the buildup of amyloid plaques typically associated with Alzheimer's disease. However, the relationship between these brain proteins and memory performance varied across groups, suggesting that Alzheimer's biomarkers may not tell the full story for everyone.
The findings come from the Health and Aging Brain Study–Health Disparities ( HABS-HD ), one of the largest and most diverse brain-imaging studies of aging in the US and were made possible by advanced PET brain scans that can detect abnormal protein buildup years before symptoms appear.
"Most Alzheimer's research has been based on non-Hispanic white participants, and our results show that we can't assume those patterns apply equally to everyone," said Koral V. Wheeler, MS, lead author of the study and PhD candidate at the Stevens INI. "If we want to advance precision medicine efforts for all communities, we need to understand how these brain markers behave across diverse populations."
Alzheimer's disease is characterized by the buildup of two proteins in the brain: amyloid beta, which forms plaques, and tau, which forms tangles that disrupt communication among brain cells. Tau accumulation in the medial temporal lobe, a region critical for memory, is considered an early warning sign of disease progression.
Using a newer generation tau PET tracer, the research team examined brain scans and memory test results from more than 1,500 adults who were cognitively normal or had mild cognitive impairment. A tau PET tracer is a specialized radioactive imaging agent used in PET scans to detect and visualize the accumulation of abnormal tau protein tangles in the brain. While higher tau levels were linked to worse memory overall, amyloid buildup strengthened this link only in non-Hispanic white and Hispanic participants, not in Black participants.
"This suggests that memory changes in Black adults may be influenced more strongly by factors beyond amyloid and tau alone," said Meredith N. Braskie, PhD , senior author of the study and assistant professor of neurology. "Vascular health, the presence of other health conditions, life-long stress exposure, and other social factors may play a prominent role and deserve closer study."
The study also found that some of the observed differences in tau levels may have reflected limitations in the scan itself, rather than true biological differences. In some cases, the tracer can produce signals in nearby areas that are not actually related to tau, making the images harder to interpret. This highlights the importance of carefully validating imaging tools in diverse populations.
"Studies like this are essential for improving how we interpret the earliest biological signs of Alzheimer's disease," said Arthur W. Toga, PhD , director of the Stevens INI and co-lead of HABS-HD. "A more complete understanding of these imaging markers can help researchers better identify risk, track disease progression, and guide future prevention strategies."
These results point to different biological pathways and risk profiles for developing cognitive decline that may shape how the disease develops in different populations and which would affect how it should be detected and treated.
Future studies will follow participants over time to better understand how tau, amyloid, vascular health, genetics, and social determinants interact to influence cognitive aging across communities.
You can view an animation related to this study here .
About the study
Data for this research were obtained from the Health and Aging Brain Study–Health Disparities (HABS-HD), a multi-site effort examining Alzheimer's disease risk and resilience in racially and ethnically diverse communities. Neuroimaging data were stored and processed using infrastructure supported by the USC Mark and Mary Stevens Neuroimaging and Informatics Institute.
This work was supported by the National Institute of Aging [R01AG054073, R01AG058533, R01AG070862, P41EB015922 and U19AG078109] and the Office of The Director of the National Institutes of Health [S10OD032285].
