Five-Class Tau PET Framework Identifies More Early-Stage Positivity in Alzheimer Disease

A prospective multicenter cross-sectional study in JAMA Neurology evaluated a harmonized visual framework for staging tau PET findings as negative, low, moderate, high, or atypical. The HEAD study analysis included 681 adults aged 50–90 years, spanning cognitively unimpaired individuals to those with dementia, at nine North American and European sites. Participants underwent two to four tau PET scans, cognitive assessments, amyloid-β PET, and MRI. Clinicians performed blinded reads, with agreement between readers and tracers among the primary outcomes.

Interrater agreement ranged from κ = 0.77 to 0.85; intertracer agreement was highest between MK-6240 and flortaucipir (κ = 0.88). Among 364 cognitively unimpaired participants, the regulatory-approved binary flortaucipir framework classified 26 as tau-positive, compared with 49 using harmonized flortaucipir reads and 71 using harmonized MK-6240 reads. Among 223 participants with mild cognitive impairment, corresponding counts were 100, 123, and 142. Results converged in dementia. Increasing tau burden classes were associated with worse cognition, higher amyloid burden, and higher plasma phosphorylated tau 217.

The findings support further evaluation of standardized visual staging for diagnostic categorization and trial stratification. However, the cross-sectional design does not establish whether additional tau-positive classifications predict progression or improve treatment decisions. Only the abstract was available for this assessment.