5/28/2026
A University of Pittsburgh-led study of 775 people found a newer brain imaging tracer identified more than twice as many at-risk cases as the FDA-approved standard — with implications for who qualifies for Alzheimer's treatment.
PITTSBURGH — A newer brain imaging tracer detects tau — the toxic protein tangles most directly tied to Alzheimer's memory loss and cognitive decline — more often and at earlier disease stages than the tracer currently used in clinical practice in the United States and Europe, University of Pittsburgh School of Medicine researchers reported May 28, 2026, in The Lancet.
Tau is a protein that normally helps stabilize brain cells. In Alzheimer's disease, tau becomes misfolded and clumps into tangles inside neurons, causing cell death and the progressive cognitive decline associated with dementia. Tau tangles are among the strongest predictors of when and how severely symptoms emerge — making accurate, early detection especially important.
The study compared two radioactive compounds — called tracers — used in positron emission tomography (PET) brain scans. Each tracer binds to tau tangles in the brain and makes them visible on imaging, creating a detailed map of where and how extensively tau has spread. Unlike emerging blood-based tests that measure proteins circulating in the bloodstream, tau PET scanning provides this spatial picture of disease biology.
"Tau is the biology most closely tied to symptoms and future decline," said corresponding author Tharick Pascoal, M.D., Ph.D., associate professor of psychiatry and neurology at Pitt and a behavioral neurologist at UPMC who studies the relationship between brain biology and cognitive symptom onset. "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."
What the Study Found
University of Pittsburgh researchers coordinated a prospective multicenter study enrolling 775 participants — 682 of whom completed all procedures — at sites including Lawrence Berkeley National Laboratory, Mayo Clinic, McGill University, University of California San Francisco and others. Each participant received both tau PET tracers within a 45-day window, along with an amyloid-beta PET scan and cognitive assessments.
"Because participants received both tracer scans within a short window, we're looking at the same moment in the disease course," said co-lead author Guilherme Povala, Ph.D., postdoctoral associate at Pitt. "Differences we see reflect the tracers, not changes over time."
In a head-to-head comparison, the newer tracer MK6240 detected tau more often than Flortaucipir — the current clinical standard — across all participant groups:
- Among cognitively unimpaired adults with amyloid pathology, MK6240 identified 15% as tau-positive vs. 6% for Flortaucipir — more than twice the detection rate, corresponding to 23 additional cases per 100 people scanned.
- Among adults with mild cognitive impairment or dementia, MK6240 identified 15 additional mild cognitive impairment cases and 21 additional dementia cases per 100 people scanned compared with Flortaucipir.
Amyloid plaques and tau tangles are the two defining hallmarks of Alzheimer's disease. While many people with amyloid pathology do not develop dementia, the presence of tau tangles alongside amyloid appears to enable the downstream brain damage most closely linked to symptoms.
Flortaucipir received FDA approval in 2020 for detecting advanced tau pathology and is the standard tracer used in U.S. and European clinical practice. MK6240 is used primarily in research and clinical trial settings and has not yet received FDA approval for routine clinical use.
The choice of tracer can determine whether a patient is identified as a candidate for anti-amyloid therapy — or excluded from consideration entirely.
"People typically seek evaluation because they have memory concerns or other symptoms," said co-lead author Bruna Bellaver, Ph.D., research assistant professor of psychiatry at Pitt. "Tau PET is one tool that can help clinicians stage disease biology and make more informed decisions."
For the millions of Americans who may be in the early stages of Alzheimer's disease without knowing it, the study suggests the choice of imaging test could determine whether they are identified for emerging therapies or missed entirely. Earlier detection of dementia-related biology can give patients, families and clinicians more time to plan and evaluate treatment options.
The Lancet study is part of a longitudinal research program supported by a more than $40 million investment from the National Institute on Aging, awarded in 2021 to compare tau tracers and improve how Alzheimer's biology is measured across research and clinical settings.
Frequently Asked Questions
Q: What is a tau PET scan, and how does it work?
A: A tau PET scan uses a radioactive tracer injected before imaging that binds to tau tangles in the brain, making them visible on a positron emission tomography scan. It allows researchers and clinicians to map where tau has spread in a living patient — without surgery or a spinal fluid procedure.
Q: Can this newer tracer be used in clinical practice today?
A: Not yet. MK6240 is currently used in research and clinical trial settings. Flortaucipir — the tracer it outperformed in this study — is the only tau PET tracer with FDA approval for routine clinical use as of May 2026.
Q: Why does detecting tau early matter for treatment?
A: Tau pathology is the strongest predictor of when and how severely Alzheimer's symptoms emerge. Identifying tau earlier helps determine who may benefit from anti-amyloid therapies and ensures clinical trials enroll the right candidates — those most likely to respond to treatment.
Additional Resources
- Project Summary and Abstract
- Study Details: Longitudinal multicenter head-to-head harmonization of tau PET tracers
- Pascoal Lab
- Dementia and Cognitive Disorders | Neurology | UPMC
Authors and Funding
Authors: Additional University of Pittsburgh co-authors of this research are Firoza Z. Lussier, M.S., Livia Amaral, M.S., Guilherme Bauer-Negrini, Ph.D., Pamela C.L. Ferreira, Ph.D., Andreia Rocha, Ph.D., Emma Ruppert, M.D., Marina S. Medeiros, M.D., Cecile Tissot, Ph.D., and Dana L. Tudorascu, Ph.D. Additional co-authors are from Lawrence Berkeley National Laboratory, Houston Methodist Research Institute, Sant Pau Memory Unit, Barcelona Down Medical Center, CIBERNED, University of California San Francisco, Mayo Clinic, Brown University, Washington University in St. Louis, McGill University and University of Texas Southwestern Medical Center.
Funding and Disclosures: This research was supported by the National Institute on Aging (R01AG073267).
