Detecting amyloid positivity in early Alzheimer's disease using combinations of plasma Aβ42/Aβ40 and p-tau

Shorena Janelidze; Sebastian Palmqvist; Antoine Leuzy; Erik Stomrud; Inge M W Verberk; Henrik Zetterberg; Nicholas J Ashton; Pedro Pesini; Leticia Sarasa; José Antonio Allué; Charlotte E Teunissen; Jeffrey L Dage; Kaj Blennow; Niklas Mattsson-Carlgren; Oskar Hansson

doi:10.1002/alz.12395

Detecting amyloid positivity in early Alzheimer's disease using combinations of plasma Aβ42/Aβ40 and p-tau

Alzheimers Dement. 2022 Feb;18(2):283-293. doi: 10.1002/alz.12395. Epub 2021 Jun 20.

Authors

Shorena Janelidze¹, Sebastian Palmqvist^{1

2}, Antoine Leuzy¹, Erik Stomrud^{1

2}, Inge M W Verberk³, Henrik Zetterberg^{4

5

6

7}, Nicholas J Ashton^{4

8

9

10}, Pedro Pesini¹¹, Leticia Sarasa¹¹, José Antonio Allué¹¹, Charlotte E Teunissen³, Jeffrey L Dage¹², Kaj Blennow^{4

5}, Niklas Mattsson-Carlgren^{1

13

14}, Oskar Hansson^{1

2}

Affiliations

¹ Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
² Skåne University Hospital, Malmö, Sweden.
³ Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
⁴ Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁵ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁶ Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
⁷ UK Dementia Research Institute at UCL, London, UK.
⁸ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
⁹ King's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, London, UK.
¹⁰ NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
¹¹ Araclon Biotech Ltd., Zaragoza, Spain.
¹² Eli Lilly and Company, Indianapolis, Indiana, USA.
¹³ Department of Neurology, Skåne University Hospital, Lund, Sweden.
¹⁴ Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.

PMID: 34151519
DOI: 10.1002/alz.12395

Abstract

Introduction: We studied usefulness of combining blood amyloid beta (Aβ)42/Aβ40, phosphorylated tau (p-tau)217, and neurofilament light (NfL) to detect abnormal brain Aβ deposition in different stages of early Alzheimer's disease (AD).

Methods: Plasma biomarkers were measured using mass spectrometry (Aβ42/Aβ40) and immunoassays (p-tau217 and NfL) in cognitively unimpaired individuals (CU, N = 591) and patients with mild cognitive impairment (MCI, N = 304) from two independent cohorts (BioFINDER-1, BioFINDER-2).

Results: In CU, a combination of plasma Aβ42/Aβ40 and p-tau217 detected abnormal brain Aβ status with area under the curve (AUC) of 0.83 to 0.86. In MCI, the models including p-tau217 alone or Aβ42/Aβ40 and p-tau217 had similar AUCs (0.86-0.88); however, the latter showed improved model fit. The models were implemented in an online application providing individualized risk assessments (https://brainapps.shinyapps.io/PredictABplasma/).

Discussion: A combination of plasma Aβ42/Aβ40 and p-tau217 discriminated Aβ status with relatively high accuracy, whereas p-tau217 showed strongest associations with Aβ pathology in MCI but not in CU.

Keywords: Alzheimer's disease; Aβ42/Aβ40; amyloid; blood biomarkers; neurofilament light; p-tau217.

Publication types

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

MeSH terms

Alzheimer Disease*
Amyloid
Amyloid beta-Peptides
Amyloidosis*
Biomarkers
Cognitive Dysfunction*
Humans
Peptide Fragments
Positron-Emission Tomography / methods
tau Proteins

Substances

Amyloid
Amyloid beta-Peptides
Biomarkers
Peptide Fragments
amyloid beta-protein (1-42)
tau Proteins