Two hallmark brain changes of Alzheimer’s disease are amyloid plaques and tau tangles, abnormal protein buildups that are closely tied to the disease process.
Until recently, doctors usually needed expensive brain scans or spinal fluid tests to confirm whether Alzheimer’s-related changes were present in the brain. Blood tests that measure Alzheimer’s biomarkers are now beginning to change that picture, particularly in specialty care settings for people who already have cognitive symptoms.
In the new study, healthy adults with the highest levels of tau in their blood were also more likely to develop cognitive impairment over the next five years — suggesting these tests may one day be able to screen for future risk.
“This is an exciting study because it represents another step toward precision medicine in Alzheimer’s disease,” says Kaitlin Seibert, MD, a behavioral neurologist at Cleveland Clinic’s Center for Brain Health in Ohio, who wasn’t involved in the study.
Healthy Adults With This Biomarker Had Higher 5-Year Risk of Later Alzheimer’s Diagnosis
The study included about 2,700 cognitively unimpaired older adults from six long-term studies in North America, Japan, and Australia. Participants had blood tests at the beginning of the study to measure p-tau217, a biomarker of Alzheimer’s disease. They also received PET scans to measure amyloid, which can clump into plaques between brain cells, disrupting how they function and contributing to the brain changes seen in Alzheimer’s disease.
Over the next five years or so, nearly 480 participants developed cognitive impairment or dementia. Researchers calculated that higher p-tau217 levels at the beginning of the study were consistently linked with greater risk, even after adjusting for amyloid buildup.
The five-year risk estimates for cognitive decline were:
- 12 percent for people with low p-tau217 levels
- 15 percent for people with intermediate levels
- 24 percent for people with high levels
- 38 percent for people with very high levels
The study also estimated the 10-year risk, which reached 78 percent in the very-high p-tau217 group. But the authors cautioned that the 10-year numbers are less certain, because only 5 percent of participants were followed that long.
“The main takeaway of our work is that very high levels of plasma p-tau217 can provide meaningful information about future risk of cognitive impairment in older adults who show no signs of memory or cognitive issues,” says first author Rachel Buckley, PhD, an associate professor of neurology at Harvard Medical School in Boston.
Why This Could Matter for Alzheimer’s Prevention Research
Current guidance from the Alzheimer’s Association focuses on using these tests as part of a diagnostic workup for suspected Alzheimer’s disease in specialized care, not as a screening tool for healthy adults.
“While clinicians are beginning to use blood tests to help diagnose Alzheimer’s disease after memory problems begin, this research takes the next step by asking whether these same tests can estimate who is most likely to develop cognitive problems years before symptoms even appear,” says Dr. Seibert.
The findings are promising because they may help researchers get closer to individualized risk estimates: not just whether Alzheimer’s-related brain changes are present, but how likely someone may be to develop cognitive problems over the next several years.
That distinction matters for prevention trials. If researchers are testing whether an early treatment can delay or prevent symptoms, they need to enroll people who are more likely to develop cognitive impairment during the study period. A blood test could be a more practical way to identify people than relying solely on brain scans or spinal fluid tests.
“This study reflects the remarkable momentum in Alzheimer’s disease research. As prevention trials in preclinical Alzheimer’s disease gain momentum, the field is shifting from reacting to Alzheimer’s disease after symptoms develop toward identifying the disease earlier, when future treatments may have the greatest opportunity to make a difference,” says Seibert.
Why the Test Isn’t Ready for Healthy Adults
The authors caution that the findings shouldn’t be interpreted as support for routine p-tau217 screening in people without cognitive impairment symptoms. The reason is simple: There is no clear medical action for a cognitively healthy person who learns they have elevated p-tau217.
“While it may be tempting to try to estimate someone’s biological risk, we don’t yet have enough evidence that widespread screening improves health or changes what we recommend for most people,” says Seibert. As prevention therapies continue to develop, that recommendation could change, she adds.
The results also aren’t ready to predict one person’s future. The low, intermediate, high, and very high categories were created for research, but clinically useful cutoffs for cognitively healthy adults still need to be established. The models also couldn’t fully account for vascular disease, risk of death, or other brain conditions that can contribute to cognitive impairment.
“Advances like this often begin in the research setting, require careful validation in clinical practice, and ultimately depend on healthcare systems being able to implement them safely and equitably for everyone who may benefit,” says Siebert.
Questions Still Remain
While this is an exciting and important first step, moving from research to everyday clinical care takes time, says Seibert.
“We still need to understand how other medical conditions affect these blood tests. For example, kidney disease can influence biomarker levels, meaning the same result may not mean the same thing for every patient,” she says.
There also needs to be longer-term studies to better understand what an elevated p-tau217 level means over 10 or even 20 years, since most people in this study were followed for about five years, says Seibert.
“Another intriguing finding was that men appeared more likely than women to develop cognitive impairment during the study,” Siebert says. “That observation deserves further investigation before we know whether it reflects true biological differences.”
Proteins such as p-tau217 are an important piece of the Alzheimer’s puzzle, but they are not the whole picture, she says. “Alzheimer’s disease is complex, and blood biomarkers will ultimately be one part of a comprehensive approach to prevention, diagnosis, and treatment,” says Seibert.
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