A new system for reading tau PET brain scans in Alzheimer's disease performs consistently across four different radioactive tracers and detects 1.9 to 2.7 times more early-stage cases than the only regulator-approved binary test
A new system for reading tau PET brain scans in Alzheimer's disease performs consistently across four different radioactive tracers and detects 1.9 to 2.7 times more early-stage cases than the only regulator-approved binary test
On September 21, the HEAD study team, spanning nine clinical sites in North America and Europe, published its results: 681 participants underwent two to four tau PET brain scans with different tracers, and from this data the team built a unified five-class severity scale. Three physicians read the scans independently, blinded to one another's ratings and to patient data.
Tau PET is a method in which a mildly radioactive tracer compound is injected into the bloodstream. The tracer binds to damaged tau protein in the brain, making it visible on the scan. Tau is one of two hallmark features of Alzheimer's disease alongside amyloid plaques, but it tracks more closely with memory decline than amyloid does, which makes it more important for selecting participants for clinical trials. The regulator-approved method for reading these scans works only for one tracer, flortaucipir, and is deliberately tuned for specificity: it almost never labels a healthy brain as diseased, but for exactly that reason it misses early-stage pathology, the stage where treatments are most effective.
Tarik Bhatt Pascoal and Suzanne Baker have been working on this problem since 2020; the U.S. National Institute on Aging committed $41 million over five years to fund it. In May the same team showed that the tracer MK-6240 roughly doubles flortaucipir's sensitivity, but each tracer has its own binding profile, so their scans cannot be directly compared. What was needed was a common language for all four. Amyloid PET already has one: in August, the FDA authorized converting amyloid scans from three tracers onto a single scale.
Tau spreads through the brain in a predictable pattern: it first affects deep memory structures, then neighboring cortical regions. The threshold for "normal" was calculated from scans of roughly fifty healthy individuals with no amyloid, imaged with all four tracers. The brain was divided into seven regions ordered by the sequence in which tau typically invades them, producing a ladder of classes: no region affected means "negative"; only the earliest regions affected means "low" stage; middle regions added means "moderate"; late regions added means "high"; middle or late regions affected without the early ones is a rare "atypical" pattern. A free web tool walks the clinician through the regions and assigns the class automatically.
Different physicians nearly always agreed on the same class, and different tracers applied to the same brain produced similar results. Compared with the binary test, the new scale identified 1.9 to 2.7 times more tau-positive cases among cognitively unimpaired individuals and 1.2 to 1.4 times more among those with mild cognitive impairment; at the dementia stage the two methods converged. The team then checked whether these additional detections were false positives: individuals whom the new scale classified as positive but the old test called negative had higher amyloid levels and higher p-tau217 (a blood-based marker of tau pathology) than individuals negative on both scales. This confirms that what the new scale is picking up is genuine early pathology. Memory test scores were nearly identical between the "negative" and "low" classes, but beyond that they dropped in a stepwise fashion: 2.5 to 3.3 points from low to moderate, and another 4.4 to 4.6 points from moderate to high.
"Tau is the biology most closely linked to symptoms and to future decline. If we can detect tau earlier and stage it more precisely, we can better identify who is truly on an Alzheimer's trajectory. That matters for clinical trials right now and could influence clinical decisions once new treatments become available," Pascoal said in May when presenting the previous phase of the same program.