Abstract
Introduction: Neocortical 3R4R (3-repeat/4-repeat) tau aggregates are rarely observed in the absence of amyloid beta (Aβ). 18F-MK6240 binds specifically to the 3R4R form of tau that is characteristic of Alzheimer's disease (AD). We report four cases with negative Aβ, but positive tau positron emission tomography (PET) findings. Methods: All Australian Imaging, Biomarkers and Lifestyle study of aging (AIBL) study participants with Aβ (18F-NAV4694) and tau (18F-MK6240) PET scans were included. Centiloid < 25 defined negative Aβ PET (Aβ–). The presence of neocortical tau was defined quantitatively and visually. Results: Aβ– 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 Aβ– participants). In these cases, the Aβ PET ligand may not be detecting the Aβ that is present.
RAS ID
44433
Document Type
Journal Article
Date of Publication
1-1-2022
Volume
14
Issue
1
Funding Information
National Health and Medical Research Council
Australian Rotary Health
Bartolina Peluso
School
School of Medical and Health Sciences / Centre for Precision Health
Grant Number
NHMRC Number: APP1140853, APP1132604, APP1151854, APP1161706, APP1191535, APP2001320, APP2007656
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Publisher
Wiley
Comments
Krishnadas, N., Doré, V., Laws, S. M., Porter, T., Lamb, F., Bozinovski, S., . . . Rowe, C. C. (2022). Exploring discordant low amyloid beta and high neocortical tau positron emission tomography cases. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 14(1), article e12326. https://doi.org/10.1002/dad2.12326