The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease

Joel Simrén; Antoine Leuzy; Thomas K Karikari; Abdul Hye; Andréa Lessa Benedet; Juan Lantero-Rodriguez; Niklas Mattsson-Carlgren; Michael Schöll; Patrizia Mecocci; Bruno Vellas; Magda Tsolaki; Iwona Kloszewska; Hilkka Soininen; Simon Lovestone; Dag Aarsland; AddNeuroMed consortium; Oskar Hansson; Pedro Rosa-Neto; Eric Westman; Kaj Blennow; Henrik Zetterberg; Nicholas J Ashton

doi:10.1002/alz.12283

The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease

Alzheimers Dement. 2021 Jul;17(7):1145-1156. doi: 10.1002/alz.12283. Epub 2021 Jan 25.

Authors

Joel Simrén^{1

2}, Antoine Leuzy³, Thomas K Karikari¹, Abdul Hye⁴, Andréa Lessa Benedet⁵, Juan Lantero-Rodriguez¹, Niklas Mattsson-Carlgren^{3

6

7}, Michael Schöll^{1

8

9}, Patrizia Mecocci¹⁰, Bruno Vellas¹¹, Magda Tsolaki¹², Iwona Kloszewska¹³, Hilkka Soininen¹⁴, Simon Lovestone¹⁵, Dag Aarsland^{4

16}; AddNeuroMed consortium; Oskar Hansson^{3

17}, Pedro Rosa-Neto⁵, Eric Westman^{18

19}, Kaj Blennow^{1

2}, Henrik Zetterberg^{1

2

9

20}, Nicholas J Ashton^{1

4

8}

Affiliations

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.

Keywords: Alzheimer's disease; magnetic resonance imaging; phosphorylated tau; plasma biomarkers.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alzheimer Disease* / blood
Alzheimer Disease* / diagnosis
Amyloid beta-Peptides / blood*
Biomarkers / blood*
Brain / pathology*
Cognitive Dysfunction* / blood
Cognitive Dysfunction* / physiopathology
Female
Gray Matter / physiopathology
Humans
Magnetic Resonance Imaging
Male
Phosphorylation
Prognosis
tau Proteins / blood*

Substances

Amyloid beta-Peptides
Biomarkers
tau Proteins