Higher African ancestry may be linked to slower rise in Alzheimer’s biomarker

A new study published in the journal Neurology provides evidence that African American individuals with higher levels of African genetic ancestry may experience a slower increase over time in a blood biomarker associated with Alzheimer’s disease. This pattern was not explained by common risk genes or other known health or lifestyle factors. The findings add nuance to ongoing efforts to understand racial disparities in Alzheimer’s disease risk and highlight the importance of studying diverse populations in dementia research.

Alzheimer’s disease and related dementias affect African American communities at higher rates than non-Hispanic White populations in the United States. Research has shown that this increased risk likely stems from a combination of factors, including differences in cardiovascular health, educational access, stress exposure, and experiences of racism. However, biological factors, including genetics, may also contribute to this disparity.

One way researchers study Alzheimer’s disease risk is through biological markers found in blood or cerebrospinal fluid. These include phosphorylated tau181 (p-Tau181), a protein associated with Alzheimer’s-related changes in the brain; glial fibrillary acidic protein (GFAP), which reflects brain inflammation; and neurofilament light (NfL), a marker of general neuronal damage.

Previous studies using self-reported racial categories have found lower levels of these biomarkers among African American individuals, but findings have been inconsistent. Importantly, most of this research has focused on cross-sectional data, capturing only a single point in time. To better understand whether patterns in biomarker change over time might differ by ancestry, the authors of the current study used genetic data to estimate the proportion of African ancestry in each participant and tracked biomarker changes over an 11-year span.

“There is a much higher risk of Alzheimer’s disease and related dementias for African American individuals than for European American individuals. But the underlying reasons are still unknown. We are hoping to improve our understanding of this topic and eventually inform prevention strategies,” explained study author Kaixiong (Calvin) Ye, an associate professor in the Department of Genetics at the University of Georgia.

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The researchers used data from the Family and Community Health Study (FACHS), a long-running study that began in the 1990s and has followed hundreds of African American families from Georgia and Iowa. For the current analysis, they focused on 573 participants with blood samples collected in either 2008 or 2019, and a subset of 225 participants who had blood drawn in both years. The average age at the 2019 follow-up was around 57 years. Most participants were women.

The team measured levels of three Alzheimer’s-related biomarkers—p-Tau181, GFAP, and NfL—from serum samples collected in 2008 and again in 2019. They used genetic data to estimate each person’s proportion of African ancestry based on comparison with a reference dataset from the 1000 Genomes Project. This allowed them to move beyond broad racial categories and assess ancestry as a continuous variable. They also excluded participants who were closely related to avoid bias in genetic comparisons.

In the cross-sectional analysis, there was no significant link between African ancestry proportion and biomarker levels at a single time point. Biomarker levels were primarily associated with age. For instance, older participants tended to have higher levels of p-Tau181, GFAP, and NfL, which is consistent with prior research. Men had higher p-Tau181 and lower GFAP levels than women, but ancestry was not a significant factor in this analysis.

The most noteworthy findings came from the longitudinal analysis. Over the 11-year span, participants with higher African ancestry showed a smaller increase in p-Tau181 levels. This pattern was statistically significant and remained stable even after accounting for a wide range of other factors, including age, sex, physical activity, body mass index, blood pressure, blood sugar levels, education, income, and diagnosed medical conditions such as diabetes or stroke. In contrast, African ancestry was not significantly associated with changes in GFAP or NfL.

The researchers also examined whether known genetic risk factors for Alzheimer’s, including the APOE e4 allele and polygenic scores derived from large studies of European ancestry populations, could explain the findings. They found no evidence that these genetic risk indicators were associated with p-Tau181 levels or their change over time in their African American sample. This suggests that genetic variants linked to Alzheimer’s in White populations may not have the same predictive value in African American populations.

When the researchers divided participants into groups based on ancestry, those in the top 20 percent for African ancestry were less likely to show increases in p-Tau181 over the 11 years compared to those in the lowest 20 percent. The trend suggested that more African ancestry may be linked to a more stable trajectory in this Alzheimer’s-related biomarker.

“The blood level of phosphorylated tau181 (p-Tau181) is a biomarker of the progression of Alzheimer’s disease,” Ye told PsyPost. “It is well-known that the p-Tau181 level increases as individuals age. The most important finding from our study is that the age-related increase in the p-Tau181 level is slower in individuals with higher African ancestry. Our finding indicates that the same p-Tau181 level has different implications for Alzheimer’s disease progression in different ancestry groups.”

“This key finding was surprising to me. Some previous studies have found that in comparison with non-Hispanic White individuals, African American individuals exhibit significantly lower blood p-Tau181 levels. These two observations indicate that the level and age-related dynamics of p-Tau181 have different indications, and thus different predictive and prognostic values, between the African American and European American individuals.”

As with all research, there are some limitations. First, the FACHS sample is relatively young, with an average age under 60 at follow-up. Alzheimer’s disease typically develops later in life, so these findings reflect early biological changes rather than clinical outcomes like cognitive decline or diagnosis. The participants were also relatively healthy, which may limit the ability to detect stronger associations.

Second, although ancestry was estimated using genetic data, ancestry itself may be associated with a range of environmental and social factors that were not fully captured in the study. For example, neighborhood conditions, diet, or exposure to discrimination could influence biological aging in ways that track with ancestry but are not necessarily genetic.

“Although we observe that association of slower change in the blood p-Tau181 level and the African ancestry proportion, we don’t know the specific factors causing this association, which could be environmental, sociocultural, behavioral, physiological, or genetic factors,” Ye said. “We have two long-term goals: 1) Figure out the factors that are driving the different prevalence of Alzheimer’s disease across ethnic groups; 2) Develop prevention strategies to lower the risk of Alzheimer’s disease for everyone.”

“There are very large genetic studies that have identified many genetic factors (or genetic variants) that are associated with the risk of Alzheimer’s disease or with the blood biomarker levels. But most of these studies were performed in individuals of European ancestry. Our study found that genetic factors identified in European samples are not as predictive in African American individuals. More genetic studies of Alzheimer’s disease and related dementia are needed in individuals of African ancestry.”

The study, “Associations of Longitudinal Changes in Blood Biomarkers of Dementia With the Proportion of Genetically Inferred African Ancestry,” was authored by Lu Wang, Huifang Xu, Ronald L. Simons, Steven R.H. Beach, Man-Kit Lei, Mei Ling Ong, Robert A. Philibert, Michelle M. Mielke, Yitang Sun, Yueqi Lu, Charleston W.K. Chiang, Burcu F. Darst, and Kaixiong Ye.