Measuring the blood biomarker plasma p-tau217 can reliably identify preclinical Alzheimer’s disease, a meta-analysis has suggested.
The US-led study found that, among older adults without cognitive impairment, circulating levels of p-tau217 could discriminate between those who had a high or low cortical amyloid burden.
Although p-tau217 assays are not approved for clinical use in the USA or UK, such tests could one day enable clinicians to identify asymptomatic patients with preclinical AD, facilitating earlier and more effective treatment, according to the paper.
The results “demonstrate robust effect sizes and good classification accuracy”, wrote the authors in JAMA Neurology [link here].
However, “currently, there are no formal guidelines for the use of blood biomarkers for AD in individuals who are asymptomatic, and until an effective secondary preventative therapy is available for asymptomatic individuals, the use of blood biomarkers in clinical settings will be for patients with clinically significant cognitive deficits,” they wrote.
The meta-analysis, included 18 observational studies and randomised clinical trials, all from 2021 – 2025, that assessed older adults without cognitive impairment who were classified as either amyloid-positive (n=2533) or -negative (n=3501), and whose p-tau219 levels were measured.
Amyloid status was determined either by amyloid-PET or cerebrospinal fluid measurement, with amyloid-PET positivity more commonly assessed with the standard uptake volume ratio (SUVR, 53% of studies) than the Centiloid scale.
The majority of the studies (82%) used Meso Scale Discovery (MSD) or Simoa platforms to determine p-tau217 levels.
The analysis suggested that there was a large effect size (1.50) when comparing the mean differences in p-tau217 levels between amyloid-positive and -negative patients.
The high area under the curve value (0.87) for p-tau217 also indicated a high accuracy for distinguishing between amyloid status.
Subgroup analysis showed that the effect size and accuracy was generally consistent across different analysis methods and study designs.
“Central role” likely in the future, but concerns in the present
Professor Joshua Grill. Source: University of California, Irvine
In a linked editorial [link here], Professor Joshua Grill, Professor of Psychiatry & Human Behaviour at the University of California, Irvine, agreed that the research suggested that “once highly effective treatments are available, plasma p-tau217 is likely to play a central role in this new clinical practice.”
However, he highlighted issues preventing current implementation, such as the limitations of the gold-standard assays for p-tau217, the lack of optimal screening thresholds, the fact that large group effect-sizes are not equivalent to individual-level diagnostic accuracy, and the possibility of high false-positive rates.
“An eventual clinical practice that includes blood biomarkers testing in older adults without cognitive impairment is also likely to be affected by external factors, as is currently the case for the clinical use of blood biomarkers in the workup of individuals with cognitive impairment,” he added.
Professor Grill also stressed the growing issue of unregulated direct-to-consumer (DTC) companies offering testing for AD, using p-tau217 and other blood biomarkers, which in many cases do not offer clinical evaluation or counselling.
“Physicians are likely to see an influx of older unimpaired adult patients bringing DTC blood biomarkers results to the clinic, asking about interpretation, prognosis, and opportunities for treatment,” he wrote.
“This could overburden available experts, delay access to diagnosis and treatment for impaired patients, and put many non-expert clinicians in challenging positions for which they lack training,” he added.
Calling for increased regulation of the industry, he concluded that, “consumers need protection from low-quality tests, unproven therapies, and the risks that accompany the label of AD.”