Plasma p217+tau versus NAV4694 amyloid and MK6240 tau PET across the Alzheimer's continuum

Vincent Doré; James D Doecke; Ziad S Saad; Gallen Triana-Baltzer; Randy Slemmon; Natasha Krishnadas; Pierrick Bourgeat; Kun Huang; Samantha Burnham; Christopher Fowler; Stephanie R Rainey-Smith; Ashley I Bush; Larry Ward; Jo Robertson; Ralph N Martins; Colin L Masters; Victor L Villemagne; Jurgen Fripp; Hartmuth C Kolb; Christopher C Rowe

doi:10.1002/dad2.12307

Plasma p217+tau versus NAV4694 amyloid and MK6240 tau PET across the Alzheimer's continuum

Alzheimers Dement (Amst). 2022 Apr 5;14(1):e12307. doi: 10.1002/dad2.12307. eCollection 2022.

Authors

Vincent Doré^{1

2}, James D Doecke³, Ziad S Saad⁴, Gallen Triana-Baltzer⁴, Randy Slemmon⁴, Natasha Krishnadas², Pierrick Bourgeat³, Kun Huang², Samantha Burnham¹, Christopher Fowler⁵, Stephanie R Rainey-Smith⁶, Ashley I Bush^{5

7}, Larry Ward⁵, Jo Robertson⁵, Ralph N Martins^{6

8

9}, Colin L Masters⁵, Victor L Villemagne^{2

10}, Jurgen Fripp³, Hartmuth C Kolb⁴, Christopher C Rowe^{2

5

7}

Affiliations

¹ The Australian e-Health Research Centre CSIRO Melbourne Victoria Australia.
² Department of Molecular Imaging & Therapy Austin Health Melbourne Victoria Australia.
³ The Australian e-Health Research Centre CSIRO Brisbane Queensland Australia.
⁴ Neuroscience Biomarkers Janssen Research and Development La Jolla California USA.
⁵ The Florey Institute of Neuroscience and Mental Health Melbourne Victoria Australia.
⁶ Edith Cowan University Joondalup Western Australia Australia.
⁷ Florey Department of Neuroscience and Mental Health The University of Melbourne Melbourne Victoria Australia.
⁸ Centre for Healthy Ageing, Health Futures Institute Murdoch University Murdoch Western Australia Australia.
⁹ McCusker Alzheimer's Research Foundation Nedlands Western Australia Australia.
¹⁰ Department of Psychiatry University of Pittsburgh Pittsburgh Pennsylvania USA.

Abstract

Introduction: We evaluated a new Simoa plasma assay for phosphorylated tau (P-tau) at aa217 enhanced by additional p-tau sites (p217+tau).

Methods: Plasma p217+tau levels were compared to ¹⁸F-NAV4694 amyloid beta (Aβ) positron emission tomography (PET) and ¹⁸F-MK6240 tau PET in 174 cognitively impaired (CI) and 223 cognitively unimpaired (CU) participants.

Results: Compared to Aβ- CU, the plasma levels of p217+tau increased 2-fold in Aβ+ CU and 3.5-fold in Aβ+ CI. In Aβ- the p217+tau levels did not differ significantly between CU and CI. P217+tau correlated with Aβ centiloids P = .67 (CI, P = .64; CU, P = .45) and tau SUVR_MT P = .63 (CI, P = .69; CU, P = .34). Area under curve (AUC) for Alzheimer's disease (AD) dementia versus Aβ- CU was 0.94, for AD dementia versus other dementia was 0.93, for Aβ+ versus Aβ- PET was 0.89, and for tau+ versus tau- PET was 0.89.

Discussion: Plasma p217+tau levels elevate early in the AD continuum and correlate well with Aβ and tau PET.

Keywords: Alzheimer's disease; Aβ imaging; amyloid imaging; amyloid plaque; blood biomarkers; blood diagnostic for Alzheimer's disease; paired helical filaments; phosphorylated tau; plasma P‐tau217; positron emission tomography; tau imaging.