Exploring discordant low amyloid beta and high neocortical tau positron emission tomography cases

Introduction: Neocortical 3R4R (3-repeat/4-repeat) tau aggregates are rarely observed in the absence of amyloid beta (A beta). F-18-M K6240 binds specifically to the 3R4R form of tau that is characteristic of Alzheimer's disease (AD). We report four cases with negative A beta, but positive tau positron emission tomography (PET) findings. Methods: All Australian Imaging, Biomarkers and Lifestyle study of aging (AIBL) study participants with A beta (F-18-NAV4694) and tau (F-18-M K6240) PET scans were included. Centiloid <25 defined negative A beta PET (A beta-). The presence of neocortical tau was defined quantitatively and visually. Results:A beta- PET was observed in 276 participants. Four of these participants (one cognitively unimpaired [CU], two mild cognitive impairment [MCI], one AD) had tau tracer retention in a pattern consistent with Braak tau stages V to VI. Fluid biomarkers supported a diagnosis of AD. In silico analysis of APP, PSEN1, PSEN2, and MAPT genes did not identify relevant functional mutations. Discussion: Discordant cases were infrequent (1.4% of all A beta- participants). In these cases, the A beta PET ligand may not be detecting the A beta that is present.