Joel Simrén1,2, Antoine Leuzy3, Thomas K Karikari1, Abdul Hye4, Andréa Lessa Benedet5, Juan Lantero-Rodriguez1, Niklas Mattsson-Carlgren3,6,7, Michael Schöll1,8,9, Patrizia Mecocci10, Bruno Vellas11, Magda Tsolaki12, Iwona Kloszewska13, Hilkka Soininen14, Simon Lovestone15, Dag Aarsland4,16, Oskar Hansson3,17, Pedro Rosa-Neto5, Eric Westman18,19, Kaj Blennow1,2, Henrik Zetterberg1,2,9,20, Nicholas J Ashton1,4,8. 1. Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. 2. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden. 3. Clinical Memory Research Unit, Lund University, Malmö, Sweden. 4. Department of Old Age Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. 5. Translational Neuroimaging Laboratory, McGill University, Montréal, Canada. 6. Department of Neurology, Skåne University Hospital, Lund, Sweden. 7. Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden. 8. Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden. 9. Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK. 10. Department of Medicine, Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy. 11. CHU Toulouse, Toulouse, France. 12. Aristotle University of Thessaloniki, Thessaloniki, Greece. 13. Medical University of Lodz, Lodz, Poland. 14. Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland. 15. University of Oxford, Oxford, UK. 16. Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway. 17. Memory Clinic, Skåne University Hospital, Malmö, Sweden. 18. Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden. 19. Department of Neuroimaging, Centre for Neuroimaging Sciences, Psychology and Neuroscience, King's College London, Institute of Psychiatry, London, UK. 20. UK Dementia Research Institute at UCL, London, UK.
Abstract
INTRODUCTION: This study investigated the diagnostic and disease-monitoring potential of plasma biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia and cognitively unimpaired (CU) individuals. METHODS: Plasma was analyzed using Simoa assays from 99 CU, 107 MCI, and 103 AD dementia participants. RESULTS: Phosphorylated-tau181 (P-tau181), neurofilament light, amyloid-β (Aβ42/40), Total-tau and Glial fibrillary acidic protein were altered in AD dementia but P-tau181 significantly outperformed all biomarkers in differentiating AD dementia from CU (area under the curve [AUC] = 0.91). P-tau181 was increased in MCI converters compared to non-converters. Higher P-tau181 was associated with steeper cognitive decline and gray matter loss in temporal regions. Longitudinal change of P-tau181 was strongly associated with gray matter loss in the full sample and with Aβ measures in CU individuals. DISCUSSION: P-tau181 detected AD at MCI and dementia stages and was strongly associated with cognitive decline and gray matter loss. These findings highlight the potential value of plasma P-tau181 as a non-invasive and cost-effective diagnostic and prognostic biomarker in AD.
INTRODUCTION: This study investigated the diagnostic and disease-monitoring potential of plasma biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia and cognitively unimpaired (CU) individuals. METHODS: Plasma was analyzed using Simoa assays from 99 CU, 107 MCI, and 103 AD dementiaparticipants. RESULTS: Phosphorylated-tau181 (P-tau181), neurofilament light, amyloid-β (Aβ42/40), Total-tau and Glial fibrillary acidic protein were altered in AD dementia but P-tau181 significantly outperformed all biomarkers in differentiating AD dementia from CU (area under the curve [AUC] = 0.91). P-tau181 was increased in MCI converters compared to non-converters. Higher P-tau181 was associated with steeper cognitive decline and gray matter loss in temporal regions. Longitudinal change of P-tau181 was strongly associated with gray matter loss in the full sample and with Aβ measures in CU individuals. DISCUSSION: P-tau181 detected AD at MCI and dementia stages and was strongly associated with cognitive decline and gray matter loss. These findings highlight the potential value of plasma P-tau181 as a non-invasive and cost-effective diagnostic and prognostic biomarker in AD.
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Authors: Thomas K Karikari; Nicholas J Ashton; Gunnar Brinkmalm; Wagner S Brum; Andréa L Benedet; Laia Montoliu-Gaya; Juan Lantero-Rodriguez; Tharick Ali Pascoal; Marc Suárez-Calvet; Pedro Rosa-Neto; Kaj Blennow; Henrik Zetterberg Journal: Nat Rev Neurol Date: 2022-05-18 Impact factor: 44.711
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Authors: N J Ashton; A Leuzy; T K Karikari; N Mattsson-Carlgren; A Dodich; M Boccardi; J Corre; A Drzezga; A Nordberg; R Ossenkoppele; H Zetterberg; K Blennow; G B Frisoni; V Garibotto; O Hansson Journal: Eur J Nucl Med Mol Imaging Date: 2021-03-06 Impact factor: 9.236
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Authors: Nicholas J Ashton; Marc Suárez-Calvet; Thomas K Karikari; Juan Lantero-Rodriguez; Anniina Snellman; Mathias Sauer; Joel Simrén; Carolina Minguillon; Karine Fauria; Kaj Blennow; Henrik Zetterberg Journal: Alzheimers Dement (Amst) Date: 2021-06-02