Tau positron emission tomography in patients with cognitive impairment and suspected Alzheimer's disease

Abstract

Alzheimer's disease (AD) is diagnosed by the presence of both amyloid β and tau proteins. Recent advances in molecular PET imaging have made it possible to assess the accumulation of these proteins in the living brain. PET ligands have been developed that bind to 3R/4R tau in AD, but not to 3R tau or 4R tau alone. Of the first-generation PET ligands, ¹⁸F-flortaucipir has recently been approved by the Food and Drug Administration. Several second-generation PET probes with less off-target binding have been developed and are being applied clinically. Visual interpretation of tau PET should be based on neuropathological neurofibrillary tangle staging instead of a simple positive or negative classification. Four visual read classifications have been proposed: "no uptake," "medial temporal lobe (MTL) only," "MTL AND," and "outside MTL." As an adjunct to visual interpretation, quantitative analysis has been proposed using MRI-based native space FreeSurfer parcellations. The standardized uptake value ratio of the target area is measured using the cerebellar gray matter as a reference region. In the near future, the Centiloid scale of tau PET is expected to be used as a harmonized value for standardizing each analytical method or PET ligand used, similar to amyloid PET.

Keywords: Alzheimer’s disease; PET; amyloid; tau.

Fig. 1.

Tau PET using ¹⁸F-MK6240 in a woman with AD in her early 70s The present study was approved by the certified Clinical Research Review Board at the National Institutes for Quantum Science and Technology, and all subjects or their legal representatives gave written informed consent. This study was registered in the Japan Registry of Clinical Trials (jRCTs 031210318). a. Visual interpretation with classification of “MTL AND” at Braak stage IV. Tau accumulation in MTL showed “hook-like” pattern in sagittal sections of PET and FUSION images (arrows). b. SUVR measures using FreeSurfer parcellation. Right and left mesial temporal masks (pink) showed SUVRs of 2.21 and 1.69, respectively with a reference mask of entire cerebellar gray matter (green).