Head-to-head comparison of amplified plasmonic exosome Aβ42 platform and single-molecule array immunoassay in a memory clinic cohort
Tomotaka Tanaka
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Clinical Imaging Research Centre, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Department of Neurology, National Cerebral and Cardiovascular Center, Osaka, Japan
Contribution: Conceptualization (lead), Data curation (lead), Formal analysis (lead), Investigation (lead), Methodology (lead), Writing - original draft (lead)
Search for more papers by this authorJoyce Chong Ruifen
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Contribution: Conceptualization (supporting), Data curation (supporting), Methodology (supporting)
Search for more papers by this authorYing-Hwey Nai
Clinical Imaging Research Centre, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Contribution: Data curation (supporting), Investigation (supporting), Methodology (supporting), Supervision (supporting), Writing - review & editing (supporting)
Search for more papers by this authorChin Hong Tan
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Division of Psychology, Nanyang Technological University, Singapore, Singapore
Contribution: Conceptualization (supporting), Formal analysis (supporting), Investigation (supporting), Writing - review & editing (supporting)
Search for more papers by this authorCarine Z. J. Lim
Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore
Institute for Health Innovation and Technology, National University of Singapore, Singapore, Singapore
Contribution: Data curation (supporting), Methodology (supporting), Writing - original draft (supporting)
Search for more papers by this authorYan Zhang
Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore
Contribution: Data curation (supporting)
Search for more papers by this authorMary C. Stephenson
Clinical Imaging Research Centre, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Contribution: Data curation (supporting), Methodology (supporting), Writing - review & editing (supporting)
Search for more papers by this authorSaima Hilal
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
Contribution: Conceptualization (supporting), Data curation (supporting), Formal analysis (supporting), Investigation (supporting), Methodology (supporting), Writing - review & editing (supporting)
Search for more papers by this authorFrancis N. Saridin
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Contribution: Data curation (supporting), Formal analysis (supporting), Methodology (supporting), Writing - original draft (supporting), Writing - review & editing (supporting)
Search for more papers by this authorBibek Gyanwali
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Contribution: Conceptualization (supporting), Data curation (supporting), Formal analysis (supporting), Investigation (supporting), Writing - review & editing (supporting)
Search for more papers by this authorSteven Villaraza
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Contribution: Conceptualization (supporting), Data curation (supporting), Formal analysis (supporting), Writing - review & editing (supporting)
Search for more papers by this authorEdward G. Robins
Clinical Imaging Research Centre, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Singapore Bioimaging Consortium, Agency for Science, A*Star, Singapore, Singapore
Contribution: Methodology (supporting), Writing - original draft (supporting), Writing - review & editing (supporting)
Search for more papers by this authorMasafumi Ihara
Department of Neurology, National Cerebral and Cardiovascular Center, Osaka, Japan
Contribution: Writing - original draft (supporting), Writing - review & editing (supporting)
Search for more papers by this authorMichael Schöll
Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden
Contribution: Conceptualization (supporting), Data curation (supporting), Writing - review & editing (supporting)
Search for more papers by this authorHenrik Zetterberg
Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK
UK Dementia Research Institute at UCL, London, UK
Contribution: Conceptualization (equal), Data curation (supporting), Methodology (supporting), Writing - original draft (supporting), Writing - review & editing (supporting)
Search for more papers by this authorKaj Blennow
Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Contribution: Conceptualization (supporting), Investigation (supporting), Writing - original draft (supporting), Writing - review & editing (supporting)
Search for more papers by this authorNicholas J. Ashton
Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden
Maurice Wohl Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
NIHR Biomedical Research Centre for Mental Health, Biomedical Research Unit for Dementia at South London, and Maudsley NHS Foundation, London, UK
Contribution: Conceptualization (supporting), Data curation (supporting), Investigation (supporting), Writing - original draft (supporting), Writing - review & editing (supporting)
Search for more papers by this authorHuilin Shao
Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore
Institute for Health Innovation and Technology, National University of Singapore, Singapore, Singapore
Contribution: Data curation (supporting), Methodology (supporting), Writing - original draft (supporting), Writing - review & editing (supporting)
Search for more papers by this authorCorresponding Author
Anthonin Reilhac
Clinical Imaging Research Centre, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Correspondence
Christopher Chen, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, MD3, 16 Medical Drive, Level 4, #04-01, Singapore 117600, Singapore.
Email: [email protected]
Anthonin Reilhac, Clinical Imaging Research Centre, Yong Loo Lin School of Medicine, National University of Singapore, Centre for Translational Medicine (MD6), 14 Medical Drive, #B1-01, Singapore 117599, Singapore.
Email: [email protected]
Contribution: Conceptualization (lead), Data curation (lead), Formal analysis (lead), Investigation (lead), Methodology (lead), Supervision (lead), Visualization (lead), Writing - original draft (lead), Writing - review & editing (lead)
Search for more papers by this authorCorresponding Author
Christopher Chen
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Correspondence
Christopher Chen, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, MD3, 16 Medical Drive, Level 4, #04-01, Singapore 117600, Singapore.
Email: [email protected]
Anthonin Reilhac, Clinical Imaging Research Centre, Yong Loo Lin School of Medicine, National University of Singapore, Centre for Translational Medicine (MD6), 14 Medical Drive, #B1-01, Singapore 117599, Singapore.
Email: [email protected]
Contribution: Conceptualization (lead), Data curation (lead), Formal analysis (lead), Funding acquisition (lead), Investigation (lead), Methodology (lead), Supervision (lead), Writing - original draft (lead), Writing - review & editing (lead)
Search for more papers by this authorTomotaka Tanaka
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Clinical Imaging Research Centre, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Department of Neurology, National Cerebral and Cardiovascular Center, Osaka, Japan
Contribution: Conceptualization (lead), Data curation (lead), Formal analysis (lead), Investigation (lead), Methodology (lead), Writing - original draft (lead)
Search for more papers by this authorJoyce Chong Ruifen
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Contribution: Conceptualization (supporting), Data curation (supporting), Methodology (supporting)
Search for more papers by this authorYing-Hwey Nai
Clinical Imaging Research Centre, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Contribution: Data curation (supporting), Investigation (supporting), Methodology (supporting), Supervision (supporting), Writing - review & editing (supporting)
Search for more papers by this authorChin Hong Tan
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Division of Psychology, Nanyang Technological University, Singapore, Singapore
Contribution: Conceptualization (supporting), Formal analysis (supporting), Investigation (supporting), Writing - review & editing (supporting)
Search for more papers by this authorCarine Z. J. Lim
Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore
Institute for Health Innovation and Technology, National University of Singapore, Singapore, Singapore
Contribution: Data curation (supporting), Methodology (supporting), Writing - original draft (supporting)
Search for more papers by this authorYan Zhang
Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore
Contribution: Data curation (supporting)
Search for more papers by this authorMary C. Stephenson
Clinical Imaging Research Centre, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Contribution: Data curation (supporting), Methodology (supporting), Writing - review & editing (supporting)
Search for more papers by this authorSaima Hilal
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
Contribution: Conceptualization (supporting), Data curation (supporting), Formal analysis (supporting), Investigation (supporting), Methodology (supporting), Writing - review & editing (supporting)
Search for more papers by this authorFrancis N. Saridin
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Contribution: Data curation (supporting), Formal analysis (supporting), Methodology (supporting), Writing - original draft (supporting), Writing - review & editing (supporting)
Search for more papers by this authorBibek Gyanwali
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Contribution: Conceptualization (supporting), Data curation (supporting), Formal analysis (supporting), Investigation (supporting), Writing - review & editing (supporting)
Search for more papers by this authorSteven Villaraza
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Contribution: Conceptualization (supporting), Data curation (supporting), Formal analysis (supporting), Writing - review & editing (supporting)
Search for more papers by this authorEdward G. Robins
Clinical Imaging Research Centre, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Singapore Bioimaging Consortium, Agency for Science, A*Star, Singapore, Singapore
Contribution: Methodology (supporting), Writing - original draft (supporting), Writing - review & editing (supporting)
Search for more papers by this authorMasafumi Ihara
Department of Neurology, National Cerebral and Cardiovascular Center, Osaka, Japan
Contribution: Writing - original draft (supporting), Writing - review & editing (supporting)
Search for more papers by this authorMichael Schöll
Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden
Contribution: Conceptualization (supporting), Data curation (supporting), Writing - review & editing (supporting)
Search for more papers by this authorHenrik Zetterberg
Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK
UK Dementia Research Institute at UCL, London, UK
Contribution: Conceptualization (equal), Data curation (supporting), Methodology (supporting), Writing - original draft (supporting), Writing - review & editing (supporting)
Search for more papers by this authorKaj Blennow
Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Contribution: Conceptualization (supporting), Investigation (supporting), Writing - original draft (supporting), Writing - review & editing (supporting)
Search for more papers by this authorNicholas J. Ashton
Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden
Maurice Wohl Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
NIHR Biomedical Research Centre for Mental Health, Biomedical Research Unit for Dementia at South London, and Maudsley NHS Foundation, London, UK
Contribution: Conceptualization (supporting), Data curation (supporting), Investigation (supporting), Writing - original draft (supporting), Writing - review & editing (supporting)
Search for more papers by this authorHuilin Shao
Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore
Institute for Health Innovation and Technology, National University of Singapore, Singapore, Singapore
Contribution: Data curation (supporting), Methodology (supporting), Writing - original draft (supporting), Writing - review & editing (supporting)
Search for more papers by this authorCorresponding Author
Anthonin Reilhac
Clinical Imaging Research Centre, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Correspondence
Christopher Chen, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, MD3, 16 Medical Drive, Level 4, #04-01, Singapore 117600, Singapore.
Email: [email protected]
Anthonin Reilhac, Clinical Imaging Research Centre, Yong Loo Lin School of Medicine, National University of Singapore, Centre for Translational Medicine (MD6), 14 Medical Drive, #B1-01, Singapore 117599, Singapore.
Email: [email protected]
Contribution: Conceptualization (lead), Data curation (lead), Formal analysis (lead), Investigation (lead), Methodology (lead), Supervision (lead), Visualization (lead), Writing - original draft (lead), Writing - review & editing (lead)
Search for more papers by this authorCorresponding Author
Christopher Chen
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Correspondence
Christopher Chen, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, MD3, 16 Medical Drive, Level 4, #04-01, Singapore 117600, Singapore.
Email: [email protected]
Anthonin Reilhac, Clinical Imaging Research Centre, Yong Loo Lin School of Medicine, National University of Singapore, Centre for Translational Medicine (MD6), 14 Medical Drive, #B1-01, Singapore 117599, Singapore.
Email: [email protected]
Contribution: Conceptualization (lead), Data curation (lead), Formal analysis (lead), Funding acquisition (lead), Investigation (lead), Methodology (lead), Supervision (lead), Writing - original draft (lead), Writing - review & editing (lead)
Search for more papers by this authorAnthonin Reilhac and Christopher Chen contributed equally.
Abstract
Background and purpose
Various blood biomarkers reflecting brain amyloid-β (Aβ) load have recently been proposed with promising results. However, to date, no comparative study amongst blood biomarkers has been reported. Our objective was to examine the diagnostic performance and cost effectiveness of three blood biomarkers on the same cohort.
Methods
Using the same cohort (n = 68), the performances of the single-molecule array (Simoa) Aβ40, Aβ42, Aβ42/Aβ40 and the amplified plasmonic exosome (APEX) Aβ42 blood biomarkers were compared using amyloid positron emission tomography (PET) as the reference standard. The extent to which these blood tests can reduce the recruitment cost of clinical trials was also determined by identifying amyloid positive (Aβ+) participants.
Results
Compared to Simoa biomarkers, APEX-Aβ42 showed significantly higher correlations with amyloid PET retention values and excellent diagnostic performance (sensitivity 100%, specificity 93.3%, area under the curve 0.995). When utilized for clinical trial recruitment, our simulation showed that pre-screening with blood biomarkers followed by a confirmatory amyloid PET imaging would roughly half the cost (56.8% reduction for APEX-Aβ42 and 48.6% for Simoa-Aβ42/Aβ40) compared to the situation where only PET imaging is used. Moreover, with 100% sensitivity, APEX-Aβ42 pre-screening does not increase the required number of initial participants.
Conclusions
With its high diagnostic performance, APEX is an ideal candidate for Aβ+ subject identification, monitoring and primary care screening, and could efficiently enrich clinical trials with Aβ+ participants whilst halving recruitment costs.
CONFLICT OF INTEREST
HZ has served at scientific advisory boards for Wave, Samumed, CogRx and Roche Diagnostics, has given open lectures in symposia sponsored by Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. The other authors report no conflicts of interests specifically related to this paper.
Open Research
DATA AVAILABILITY STATEMENT
All data generated for this work and which support the findings are available upon reasonable request.
Supporting Information
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Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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