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

Authors

Natasha Krishnadas
Vincent Doré
Simon M. Laws, Edith Cowan UniversityFollow
Tenielle Porter, Edith Cowan UniversityFollow
Fiona Lamb
Svetlana Bozinovski
Victor L. Villemagne, Edith Cowan UniversityFollow
Christopher C. Rowe

Author Identifier

Simon M. Laws

https://orcid.org/0000-0002-4355-7082

Tenielle Porter

https://orcid.org/0000-0002-7887-6622

Document Type

Journal Article

Publication Title

Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring

Volume

14

Issue

1

Publisher

Wiley

School

School of Medical and Health Sciences / Centre for Precision Health

RAS ID

44433

Funders

National Health and Medical Research Council

Australian Rotary Health

Bartolina Peluso

Grant Number

NHMRC Number: APP1140853, APP1132604, APP1151854, APP1161706, APP1191535, APP2001320, APP2007656

Grant Link

http://purl.org/au-research/grants/nhmrc/GNT1161706

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

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.

DOI

10.1002/dad2.12326

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License