Summary: For decades, Alzheimer’s research has relied largely on study populations of European ancestry, leaving important questions about how the disease appears in other groups. A new, landmark USC study breaks from that one-size-fits-all model. By examining brain imaging markers in a racially and ethnically diverse cohort, researchers found notable differences in how early Alzheimer’s pathology—particularly tau tangles and amyloid plaques—appears across Black, Hispanic/Latino, and non-Hispanic White communities.
These results indicate that the biological timing and presentation of Alzheimer’s can vary by population. That variation has implications for diagnosis, the interpretation of PET and MRI scans, and the design of future treatments and clinical trials so they work equitably across groups.
Key Facts
- Population differences: The density and regional distribution of early Alzheimer’s biomarkers—amyloid and tau—differ significantly between Black, Hispanic, and non-Hispanic White participants.
- Tau disparities: Some groups showed higher burdens of tau tangles in memory-related brain regions even when amyloid levels were similar to other groups.
- Genetic and social contributors: Genetics matter, but researchers highlight social determinants of health—education, air quality, access to care, vascular health, and lifelong stress—as likely contributors to these biological differences.
- Addressing underrepresentation: The research used data from the USC Mark and Mary Stevens Neuroimaging and Informatics Institute and the HABS‑HD study, which purposely recruited a diverse sample to correct historic gaps in neuroscience research.
Source: USC
A research team at the USC Mark and Mary Stevens Neuroimaging and Informatics Institute (Stevens INI) within the Keck School of Medicine of USC reports meaningful differences in how early Alzheimer’s-related brain changes appear across racial and ethnic groups, reinforcing the need for more inclusive research and diagnostic practices.
Their peer-reviewed findings appear in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
In a large, racially and ethnically diverse sample of older adults without dementia, investigators found that Black and Hispanic participants had higher levels of tau protein in key medial temporal lobe regions—areas critical for memory—compared with non-Hispanic White participants. This elevation in tau appeared even before significant amyloid plaque accumulation in some cases. Yet the way these proteins related to cognitive performance differed across groups, indicating that common biomarker thresholds and interpretations may not apply universally.
The results come from the Health and Aging Brain Study–Health Disparities (HABS‑HD), one of the largest and most diverse PET neuroimaging studies of aging in the United States. The study relied on advanced PET tracers capable of detecting abnormal protein accumulation years before clinical symptoms arise.
“Most Alzheimer’s studies have focused on non-Hispanic White participants, and our data show those patterns can’t be assumed to hold for everyone,” said Koral V. Wheeler, MS, the study’s lead author and a PhD candidate at Stevens INI. “If precision medicine is our goal, we must understand how these imaging markers behave across diverse populations.”
Alzheimer’s disease is marked by two hallmark protein pathologies: amyloid‑beta plaques and tau tangles. Tau buildup in the medial temporal lobe is widely considered an early indicator of disease progression. Using a newer-generation tau PET tracer (18F-PI-2620), the team evaluated brain scans and memory test scores from more than 1,500 adults who were cognitively unimpaired or had mild cognitive impairment.
Overall, higher tau levels were associated with poorer memory performance. However, amyloid burden strengthened that association only in non-Hispanic White and Hispanic participants, not in Black participants. This pattern suggests that cognitive decline in some groups may be driven by additional factors beyond amyloid and tau, such as vascular health, other chronic conditions, and cumulative social and environmental stressors.
The study also identified technical challenges: in some participants the tracer produced off-target signals in nearby tissues—such as the choroid plexus or meninges—that could exaggerate apparent tau levels. After accounting for these off-target effects, some group differences in lateral temporal regions diminished. This underscores the need to validate imaging tools across diverse populations to avoid misinterpretation.
“Careful validation of PET tracers and imaging methods in diverse samples is essential,” said Arthur W. Toga, PhD, director of the Stevens INI and a co-leader of HABS‑HD. “A clearer picture of how imaging markers vary across populations will improve risk assessment, tracking of disease progression, and design of prevention strategies.”
These findings point toward different biological pathways and risk profiles that may shape how cognitive decline begins and progresses in different communities. Longitudinal follow-up of participants will be essential to untangle how tau, amyloid, vascular factors, genetics, and social determinants interact over time.
About the study
This research used data from the Health and Aging Brain Study–Health Disparities (HABS‑HD), a multi-site study focused on Alzheimer’s risk and resilience across racially and ethnically diverse communities. Neuroimaging data were managed and processed using the infrastructure of the USC Mark and Mary Stevens Neuroimaging and Informatics Institute.
Funding: The work was supported by the National Institute on Aging (grant numbers R01AG054073, R01AG058533, R01AG070862, P41EB015922, U19AG078109) and the Office of the Director of the National Institutes of Health (S10OD032285).
Key Questions Answered:
A: If our research and diagnostics are based on a single population, they may only fit that group. Many current therapies and trial designs focus on amyloid plaques. If some populations show more tau or different regional patterns of pathology, amyloid-targeted approaches might be less effective. Broadly representative research helps create diagnostic criteria and treatments that work across diverse biological backgrounds.
A: The study shows that some communities may develop symptoms earlier or with different biomarker profiles. That does not necessarily mean the disease is inherently more severe; rather, resilience and progression appear influenced by a mix of biology, vascular health, comorbidities, and lifelong social and environmental exposures.
A: PET scans and MRI remain powerful tools, but this research emphasizes that interpretation must be tailored. A biomarker level considered typical in one group might signal higher risk in another. Moving toward personalized neuro-diagnostics will improve accuracy and equity in risk detection.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full by the editorial team.
- Additional context was added by staff to clarify implications for diverse communities and future research.
About this Alzheimer’s disease research news
Author: Laura LeBlanc
Source: USC
Contact: Laura LeBlanc – USC
Image: The image is credited to Neuroscience News
Original Research: Open access.
“The relationships between ethnoracial identity, Aβ positivity, APOEε4, and medial temporal lobe tau PET” by Koral V. Wheeler et al., published in Alzheimer’s & Dementia.
DOI: 10.1002/alz.71226
Abstract
The relationships between ethnoracial identity, Aβ positivity, APOEε4, and medial temporal lobe tau PET
INTRODUCTION
Understanding how amyloid, tau, and cognition interact is essential to predicting dementia risk, yet most prior work has focused on non-Hispanic White participants. It remains unclear whether those results apply to other ethnoracial groups.
METHODS
The study evaluated relationships among amyloid‑beta positivity, the APOE ε4 allele, tau PET using 18F‑PI‑2620, and cognitive outcomes in 1,181 cognitively unimpaired adults (451 non-Hispanic White, 353 Hispanic, 377 Black) and 383 adults with mild cognitive impairment (85 non-Hispanic White, 129 Hispanic, 169 Black) enrolled in HABS‑HD.
RESULTS
Black (β = 0.28, p < 0.001) and Hispanic (β = 0.34, p < 0.001) participants had higher medial temporal lobe tau than non-Hispanic White participants; some of these differences were reduced after accounting for choroid plexus off-target binding. Hispanic participants initially showed higher lateral temporal tau, but correcting for meningeal off-target signal produced similar lateral temporal tau across groups.
DISCUSSION
The data suggest that factors beyond amyloid and tau, including vascular health and social determinants, may influence cognition among Black participants. Ethnoracial differences in off-target PI2620 binding require further investigation to ensure accurate interpretation of tau PET across diverse populations.