Plasma p-tau217 Linked to Cognitive Decline in Women: Study Findings

Plasma Tau Levels Linked to Dementia Risk in Women, Study Finds

Latest research published in JAMA Network Open suggests that higher levels of a specific protein in the blood, phosphorylated tau 217 (p-tau217), are associated with an increased risk of developing mild cognitive impairment or dementia in women. The findings underscore the potential of this blood-based biomarker for identifying individuals at higher risk, though researchers emphasize the need for further investigation, particularly in diverse populations. This discovery builds on previous studies demonstrating p-tau217’s ability to detect Alzheimer’s pathology.

Understanding the Biomarker

Phosphorylated tau 217 is a form of the tau protein, which is known to accumulate in the brains of individuals with Alzheimer’s disease and other forms of dementia. While traditionally measured through cerebrospinal fluid analysis or brain imaging, the ability to detect p-tau217 in blood offers a less invasive and more accessible method for risk assessment. The study, led by Aladdin H. Shadyab, PhD, MPH, of the University of California, San Diego, analyzed data from the Women’s Health Initiative Memory Study, following over 2,700 women aged 65 to 79 for up to 25 years.

Study Design and Key Findings

The Women’s Health Initiative Memory Study included 2,766 women (average age 69.9 years, with a diverse representation including 73.9% White, 17.9% Black, and 7.1% Hispanic/Latino participants). Participants were initially cognitively healthy and randomly assigned to receive estrogen, estrogen plus progestin, or a placebo as part of a separate hormone therapy trial. Researchers assessed the relationship between plasma p-tau217 levels and the incidence of mild cognitive impairment and dementia over the follow-up period.

The study revealed a significant association: women with higher levels of p-tau217 were more than twice as likely to develop either mild cognitive impairment or dementia. Specifically, for every one standard deviation increase in log2-transformed p-tau217 levels, the hazard ratio (HR) for incident mild cognitive impairment/dementia was 2.43 (95% CI, 2.18-2.71). This association remained significant when analyzing the risk for mild cognitive impairment alone (HR = 1.94; 95% CI, 1.71-2.2) and dementia alone (HR = 3.17; 95% CI, 2.79-3.61).

Hormone Therapy and Biomarker Interaction

Interestingly, the study as well explored the potential interaction between hormone therapy and p-tau217 levels. Researchers found that the link between p-tau217 and dementia risk was stronger in women who received estrogen plus progestin compared to those who received a placebo (HR = 4.18; 95% CI, 3.41-5.13 vs. HR = 3.07; 95% CI, 2.41-3.91; P for interaction = .04). No significant difference was observed for mild cognitive impairment or combined cognitive outcomes within this subgroup. Estrogen alone did not display a significant interaction with p-tau217 and dementia risk.

Subgroup Analysis: Age, Genetics, and Race

The association between p-tau217 and cognitive decline varied based on several factors. Women over 70 years old showed a stronger link compared to those 70 or younger (P for interaction = .04). Similarly, women carrying the APOE 4 gene, a known genetic risk factor for Alzheimer’s disease, exhibited a more pronounced association (P for interaction = .02). Perhaps most notably, the relationship differed significantly by race, with the strongest association observed in White women (P for interaction < .001).

Specifically, a significant link between mild cognitive impairment and p-tau217 was found in White women (HR = 2.16; 95% CI, 1.9-2.47; P for interaction < .001), but this was not replicated in Black women. This finding highlights the importance of considering racial differences in biomarker research and the potential for varying disease trajectories across populations.

Diagnostic Accuracy and Future Directions

The study also assessed the diagnostic accuracy of p-tau217 in predicting dementia. The biomarker demonstrated a reasonable ability to discriminate between those who would and would not develop dementia, with an area under the curve (AUC) of 72.7%. Combining p-tau217 with age further improved accuracy, particularly in White women (AUC: 72% vs. Black women, 70.4%).

“Future studies are needed to confirm these findings in men and in more diverse populations,” Shadyab told Healio. Further research is also needed to understand the underlying mechanisms driving the observed differences in biomarker associations across racial groups and hormone therapy regimens. March 13th, 2026 is World Sleep Day, a reminder of the importance of prioritizing brain health through lifestyle factors like adequate sleep.

Implications for Early Detection and Prevention

While not a diagnostic tool on its own, the study suggests that p-tau217 could be a valuable addition to the toolkit for identifying individuals at increased risk of dementia. Early detection allows for proactive management strategies, including lifestyle modifications, cognitive training, and potential participation in clinical trials. But, it’s crucial to remember that a high p-tau217 level does not guarantee the development of dementia, and further evaluation is necessary to determine an individual’s overall risk profile. The National Institute on Aging offers resources on Alzheimer’s and related dementias, including information on clinical trials and support services.

Contact Information: Aladdin H. Shadyab, PhD, MPH, can be reached at [email protected].