Plasma P-tau181 to Aβ42 ratio is associated with brain amyloid burden and hippocampal atrophy in an Asian cohort of Alzheimer's disease patients with concomitant cerebrovascular disease

Joyce R. Chong, Nicholas J. Ashton, Thomas K. Karikari, Tomotaka Tanaka, Francis N. Saridin, Anthonin Reilhac, Edward G. Robins, Ying Hwey Nai, Henri Vrooman, Saima Hilal, Henrik Zetterberg, Kaj Blennow, Mitchell K.P. Lai*, Christopher P. Chen

*Corresponding author for this work

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Abstract

Introduction: There is increasing evidence that phosphorylated tau (P-tau181) is a specific biomarker for Alzheimer's disease (AD) pathology, but its potential utility in non-White patient cohorts and patients with concomitant cerebrovascular disease (CeVD) is unknown. 

Methods: Single molecule array (Simoa) measurements of plasma P-tau181, total tau, amyloid beta (Aβ)40 and Aβ42, as well as derived ratios were correlated with neuroimaging modalities indicating brain amyloid (Aβ+), hippocampal atrophy, and CeVD in a Singapore-based cohort of non-cognitively impaired (NCI; n = 43), cognitively impaired no dementia (CIND; n = 91), AD (n = 44), and vascular dementia (VaD; n = 22) subjects. 

Results: P-tau181/Aβ42 ratio showed the highest area under the curve (AUC) for Aβ+ (AUC = 0.889) and for discriminating between AD Aβ+ and VaD Aβ− subjects (AUC = 0.903). In addition, P-tau181/Aβ42 ratio was associated with hippocampal atrophy. None of the biomarkers was associated with CeVD. 

Discussion: Plasma P-tau181/Aβ42 ratio may be a noninvasive means of identifying AD with elevated brain amyloid in populations with concomitant CeVD.

Original languageEnglish
Pages (from-to)1649-1662
Number of pages14
JournalAlzheimer's and Dementia
Volume17
Issue number10
Early online date31 Mar 2021
DOIs
Publication statusPublished - Oct 2021

Bibliographical note

Funding Information:
This study was supported by the National Medical Research Council (NMRC/CSA-SI/007/2016 to CPC and MKPL; and NMRC/CG/M006/2017, NMRC/CG/013/2013, and NMRC/CG/NUHS/2010 to CPC). NJA is supported by the Swedish Alzheimer Foundation (Alzheimerfonden), the Swedish Brain Foundation (Hj?rnfonden), the Swedish Dementia Foundation (Demensf?rbundet), and Gamla Tj?narinnor Foundation. TKK holds a research fellowship from the BrightFocus Foundation (#A2020812F) and is further supported by the Swedish Alzheimer Foundation (Alzheimerfonden; #AF-930627), the Swedish Brain Foundation (Hj?rnfonden; #FO2020-0240), the Swedish Dementia Foundation (Demensf?rbundet), the Swedish Parkinson Foundation (Parkinsonfonden; #1252/20), Gamla Tj?narinnor Foundation, the Aina (Ann) Wallstr?ms and Mary-Ann Sj?bloms Foundation, the Agneta Prytz-Folkes & G?sta Folkes Foundation (#2020-00124), the Gun and Bertil Stohnes Foundation, and the Anna Lisa and Brother Bj?rnsson's Foundation. HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the European Union's Horizon 2020 research and innovation programme under the Marie Sk?odowska-Curie grant agreement No 860197 (MIRIADE), and the UK Dementia Research Institute at UCL. KB is supported by the Swedish Research Council (#2017-00915), the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB-201809-2016615), the Swedish Alzheimer Foundation (#AF-742881), Hj?rnfonden, Sweden (#FO2017-0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986), and the European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236). The authors would like to thank the patients and their families for their participation in this study. We would also like to thank the NUS CIRC radiochemistry and QA team for the production and supply of radioligands, and specifically Dr Akbar Kulasi (quality assurance), David James Green (radioisotope production/cyclotron), Elaine Jia Hui Tan (quality control), and Mohd Fadli Bin Mohammad Noh (manufacturing) for contributing to the different aspects of the synthesis of [18F]Flutafuranol.

Publisher Copyright:
© 2021 the Alzheimer's Association

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