Cortical laminar binding of PET amyloid and tau tracers in Alzheimer disease

Neurofibrillary tau pathology and amyloid β (Aβ) plaques, characteristic lesions of Alzheimer disease (AD), show different neocortical laminar distributions. Neurofibrillary-tangle tau pathology tends to be closer to the gray matter-white matter boundary, whereas Aβ is dispersed throughout the width of the cortical ribbon. Methods: Using PET radiotracers for tau and Aβ lesions, we developed an image analysis tool to measure the distance of tracer-positive voxels from the gray matter-white matter boundary. We studied 5 AD and 5 healthy subjects with both ¹⁸F-THK5117 (tau) and ¹¹C-Pittsburgh compound B (Aβ) PET. Results: On average, tau-positive voxels were closer to the white matter than were Aβ-positive voxels. This effect was found for all AD subjects and for all regions, both before and after regionally adjusting for the nonspecific white matter binding of both tracers. The differential laminar pattern was validated through postmortem examination. Conclusion: Within cortical lamina, distance measures may be of value in testing PET tracers for their anatomic selectivity.