Plasma measures of phosphorylated tau217 (p-tau217) can accurately identify individuals in the preclinical stage of Alzheimer’s disease (AD), a new meta-analysis showed.

The results are important because the preclinical stage is when therapeutic interventions are most likely to delay or stop disease progression, investigators said.

The FDA has approved a p-tau217 blood test to use in symptomatic patients, but these new findings suggest such tests could be used to screen asymptomatic individuals once an effective preventative therapy becomes available.

“This paper is an initial indication that we can be reasonably confident in the results of p-tau217 assays in the preclinical stage,” lead author Michael Malek-Ahmadi, PhD, senior bioinformatics scientist, Banner Alzheimer’s Institute, and assistant research professor, Department of Biomedical Informatics, College of Medicine-Phoenix, The University of Arizona, both in Phoenix, told Medscape Medical News.

The findings were published online on December 1, 2025, in JAMA Neurology.

Robust Findings

Blood-based biomarkers (BBMs) can accurately detect AD and are a more convenient and cost-effective alternative to amyloid-PET imaging and cerebrospinal fluid testing. They may therefore allow for broader screening and earlier detection of pathologic changes, researchers noted.

To date, there has not been a comprehensive analysis of the effect size and classification accuracy of p-tau217 in individuals without cognitive impairment.

The meta-analysis included 18 observational studies and randomized clinical trials with 7834 individuals without cognitive impairment who were classified as either amyloid positive (2533) or amyloid negative (5301).

The mean age was 71 years for amyloid-positive participants and 68 years for amyloid-negative participants.

The analysis found a robust effect size for p-tau217 (Hedges g, 1.50; 95% CI, 1.33-1.68) and a good classification accuracy for differentiating amyloid-positive from amyloid-negative individuals (area under the curve, 0.87; 95% CI, 0.85-0.90).

Several subgroup and sensitivity analyses yielded effect sizes comparable to the main analysis, which suggests the findings “were robust to a number of possible methodological confounds,” the authors wrote.

For example, one analysis found effect sizes were nearly equal for community-based and clinic-based cohorts. Malek-Ahmadi noted patients coming into the clinic are more likely to progress faster while those recruited from the community are generally healthier and disease-free.

Another analysis found Simoa-based assays had a slightly higher effect size than MSD-based assays.

“Overall, in the bigger picture, they both perform relatively equally in terms of identifying the individuals we’re looking for,” said Malek-Ahmadi.

Early Treatment Hopes

The preclinical stage of AD, when biological markers are present but not clinical symptoms, “is the best opportunity or the best time to start treatment in order to have the best clinical outcome,” noted Malek-Ahmadi.

Many intervention trials conducted during the 2000s “likely failed because we were starting treatment far too late in the disease spectrum,” he said.

Secondary prevention trials are now under way, Malek-Ahmadi said.

“When, and if, those trials show positive results, that would indicate therapy can be started in people in the preclinical stage. So having the marker that identifies them in that stage would get them treatment as early as possible,” he said.

He predicts an effective prevention therapy that can be used in the preclinical stage will be available within 2-5 years.

The authors noted the studies included in the meta-analysis were all published in a relatively narrow time frame (2021-2025), reflecting the rapid adoption of p-tau217 in research on the detection of preclinical AD and pointing to “some level of superiority” of this p-tau assay, Malek-Ahmadi said.

In the wake of these rapid changes, evidence-based clinical guidelines were recently published that provide sensitivity and specificity values that a diagnostic blood test for AD should meet to be used in a clinical setting. The guideline does not endorse specific tests or rank them.

Patients included in the current meta-analysis were mostly highly educated and White. Another limitation was that in addition to using different assay platforms (Simoa vs MSD), included studies had different assay designs, which may have added bias.

As well, the high degree of heterogeneity in the analyses complicates the interpretation of the reported effect sizes.

Ethical Issues Raised

Despite the promising findings, some experts worry about ethical issues linked to the testing, Joshua D. Grill, PhD, Institute for Memory Impairments and Neurological Disorders, Departments of Psychiatry and Human Behavior and Neurobiology and Behavior, University of California, Irvine, wrote in an accompanying editorial.

Such issues include inadequate legal protections, lack of education and counselling, and increased AD stigma. Some experts recommend against biomarker testing in asymptomatic patients until evidence-based symptom-delaying treatments become available, Grill wrote.

With a burgeoning BBM industry, he foresees an influx of older unimpaired adult patients bringing direct-to-consumer BBM results to the clinic, asking about interpretation, prognosis, and opportunities for treatment. As previously reported by Medscape Medical News, such tests are already widely available, including some that don’t require a prescription or clinician oversight.

“This could overburden available experts, delay access to diagnosis and treatment for impaired patients, and put many nonexpert clinicians in challenging positions for which they lack training,” he wrote.

Still, Grill found the new results “compelling” and predicted plasma p-tau217 will likely play a central role in clinical practice once highly effective treatments are available.

‘Timely and Relevant’

Commenting on the findings for Medscape Medical News, Thomas R. Vidic, MD, adjunct clinical professor of neurology, Indiana University School of Medicine, South Bend, Indiana, called the study “timely and relevant,” noting that he has already discussed such a blood test with some of his asymptomatic patients.

“Before, we were relying on PET scans and lumbar punctures, but now, the discussion is much earlier in the course of an evaluation,” he said.

He agreed that the meta-analysis will help justify use of the test as a routine screening tool in asymptomatic individuals once an effective preventative therapy is available.

Also commenting for Medscape Medical News, Sheena Aurora, PhD, vice president of medical affairs for the Alzheimer’s Association and a practicing neurologist, said she’s “very excited” about p-tau217 which is proving to be “a great marker for amyloid deposition.” 

However, since there are still no approved treatments for amyloid positivity, “I don’t think these tests should be widely used.”

She takes issue with labeling individuals in the studies as “preclinical” as they may not progress.

“We actually don’t know, and we can’t assume, that all the subjects in these studies that were amyloid positive, end up developing symptoms,” she said.

For any test, Aurora believes neurologists should discuss the pros and cons with each patient before proceeding with it.

“There are so many implications and so we have to be very careful, and very scientifically rigorous,” she noted.

The study was supported by grants from the National Institute on Aging, Arizona Alzheimer’s Disease Research Center. Malek-Ahmadi reported receiving consulting fees from Biomedical Research Alliance of New York. Vidic reported having no relevant conflicts of interest. Grill reported receiving grants from the National Institute on Aging, the National Center for Advancing Translational Sciences, the Alzheimer’s Association, the BrightFocus Foundation, Eli Lilly, Biogen, Genentech, and Eisai; receiving nonfinancial support from the Alzheimer’s Association; and providing editorial services for Alzheimer’s & Dementia.