Biomarker p-tau217 Blood Test Predicts Dementia in Women as Many as 25 Years Before Symptoms Begin

A simple blood test could help identify women at increased risk of dementia up to 25 years before symptoms appear. In a long-term study, higher levels of the biomarker p-tau217 were strongly linked to later cognitive decline, highlighting the potential of blood-based testing for earlier risk assessment and prevention research.

Researchers from the University of California San Diego have found that a novel blood-based biomarker can predict a woman’s risk of developing dementia as many as 25 years before symptoms appear. The study shows that higher levels of phosphorylated tau 217 (p-tau217) — a protein linked to the brain changes seen in Alzheimer’s disease — were strongly associated with future mild cognitive impairment and dementia among older women who were cognitively healthy at baseline, meaning at the start of the study before any memory or thinking problems were detected.

“Our study suggests we may be able to identify women at elevated risk for dementia decades before symptoms emerge,” said Aladdin H. Shadyab, PhD, MPH, first author of the study and UC San Diego associate professor of public health and medicine at the Herbert Wertheim School of Public Health and Human Longevity Science and the School of Medicine. “That kind of long lead time opens the door to earlier prevention strategies and more targeted monitoring, rather than waiting until memory problems are already affecting daily life.”

The findings are based on data from 2,766 participants in the Women’s Health Initiative Memory Study, a large national study that enrolled women ages 65 to 79 in the late 1990s and followed them for up to 25 years. All women were cognitively unimpaired when they entered the study. Blood samples collected at baseline were analyzed years later to measure p-tau217, a form of tau protein that reflects early brain changes associated with Alzheimer’s disease.

Over the years of follow-up, researchers identified women who developed memory or thinking problems, including dementia. Those who had higher levels of p-tau217 in their blood at the start of the study were much more likely to develop dementia later in life. In fact, as levels of this biomarker increased, so did dementia risk. Women with the highest p-tau217 levels faced the greatest likelihood of developing dementia over the long term.

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However, the researchers also found that risk of cognitive impairment or dementia associated with higher levels of p-tau217 was not the same for everyone. For example, higher p-tau217 levels were more strongly associated with poorer cognitive outcomes among women over age 70 than those younger than 70 years at baseline and among those with the APOE ε4 genetic risk factor for Alzheimer’s disease. The study also found that p-tau217 was more predictive of dementia among women who had been randomized to estrogen plus progestin hormone therapy versus placebo. The strength of the association also differed between white and Black women, but combining p-tau217 with age improved dementia prediction similarly in both groups.

“Blood-based biomarkers like p-tau217 are especially promising because they are far less invasive and potentially more accessible than brain imaging or spinal fluid tests,” said Linda K. McEvoy, PhD, senior author of the study, senior investigator at Kaiser Permanente Washington Health Research Institute and professor emeritus at the Herbert Wertheim School of Public Health. “This is important for accelerating research into the factors that affect risk of dementia and for evaluating strategies that may reduce risk.”

Currently, blood-based biomarkers are not recommended for clinical use in people without symptoms of cognitive impairment. The authors note that additional studies are needed to determine how p-tau217 testing might be used in routine clinical care and whether early identification can meaningfully change outcomes. Future research will also explore how factors such as hormone therapy, genetics and age-related health conditions interact with plasma p-tau217 over the course of someone’s life to affect dementia risk.

“Ultimately, the goal is not just prediction,” Shadyab added, “but using that knowledge to delay or prevent dementia altogether.”

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