A new PET imaging agent identified signs of Alzheimer’s disease-related tau pathology in substantially more people than the tracer currently used in clinical practice, according to a study published in The Lancet by researchers at the University of Pittsburgh School of Medicine.

The study compared two tau PET tracers, compounds that bind to tau protein and become visible on brain scans. Researchers found that MK6240, an investigational tracer, detected tau pathology more frequently than flortaucipir, the FDA-approved tracer commonly used to identify advanced tau accumulation.

The prospective multicenter study enrolled 775 participants, with 682 completing all procedures. Participants underwent paired tau PET scans using both tracers, as well as amyloid-beta PET imaging and cognitive assessments within a 45-day period.
Among cognitively unimpaired participants who tested positive for amyloid-beta, MK6240 identified tau positivity in 15% of cases, compared with 6% for flortaucipir. In participants with cognitive impairment, MK6240 detected tau pathology in 28% of individuals, versus 16% with the standard tracer.

“Tau is the biology most closely tied to symptoms and future decline,” said Tharick Pascoal, associate professor of psychiatry and neurology at the University of Pittsburgh, and a behavioral neurologist at UPMC. “If we can detect tau earlier and stage it more precisely, we can make better decisions about who is truly on an Alzheimer’s trajectory, which matters for clinical trials now and could shape clinical decision-making as new therapies emerge.”

Researchers said the study’s head-to-head design allowed a direct comparison of tracer performance because each participant received both scans during the same stage of disease progression.

The findings add to growing evidence that tau pathology may be a stronger indicator of future cognitive decline than amyloid plaques alone. Identifying tau accumulation earlier could help researchers select participants for clinical trials and improve assessment of patients being considered for Alzheimer’s therapies.

MK6240 remains investigational and has not received FDA approval for routine clinical use. Flortaucipir is currently approved in the United States for detecting advanced tau pathology associated with Alzheimer’s disease.

The work is part of a National Institutes of Health-funded research program launched in 2021 to evaluate tau imaging agents and standardize measurement of Alzheimer’s disease biology across research and clinical settings.

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