A blood-based biomarker workflow for optimal tau-PET referral in memory clinic settings

Wagner S Brum; Nicholas C Cullen; Joseph Therriault; Shorena Janelidze; Nesrine Rahmouni; Jenna Stevenson; Stijn Servaes; Andrea L Benedet; Eduardo R Zimmer; Erik Stomrud; Sebastian Palmqvist; Henrik Zetterberg; Giovanni B Frisoni; Nicholas J Ashton; Kaj Blennow; Niklas Mattsson-Carlgren; Pedro Rosa-Neto; Oskar Hansson

doi:10.1038/s41467-024-46603-2

A blood-based biomarker workflow for optimal tau-PET referral in memory clinic settings

Nat Commun. 2024 Mar 14;15(1):2311. doi: 10.1038/s41467-024-46603-2.

Authors

Wagner S Brum^#^{1

2}, Nicholas C Cullen^#^{3

4}, Joseph Therriault^#^{5

6}, Shorena Janelidze³, Nesrine Rahmouni^{5

6}, Jenna Stevenson^{5

6}, Stijn Servaes^{5

6}, Andrea L Benedet¹, Eduardo R Zimmer^{2

5

7

8}, Erik Stomrud^{3

9}, Sebastian Palmqvist^{3

9}, Henrik Zetterberg^{1

10

11

12

13

14}, Giovanni B Frisoni¹⁵, Nicholas J Ashton^{1

16

17

18}, Kaj Blennow^{1

10}, Niklas Mattsson-Carlgren^{3

4

19}, Pedro Rosa-Neto^{5

6}, Oskar Hansson²⁰

Affiliations

¹ Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
² Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
³ Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.
⁴ Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.
⁵ McGill Centre for Studies in Aging, McGill University, Verdun, Quebec, QC, Canada.
⁶ Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Quebec, QC, Canada.
⁷ Department of Pharmacology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
⁸ Graduate Program in Biological Sciences: Pharmacology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
⁹ Memory Clinic, Skåne University Hospital, Lund, Sweden.
¹⁰ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹¹ Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
¹² UK Dementia Research Institute at UCL, London, United Kingdom.
¹³ Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
¹⁴ Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
¹⁵ Memory Center, Geneva University and University Hospital, Geneva, Switzerland.
¹⁶ King's College London, Institute of Psychiatry, Psychology and Neuroscience Maurice Wohl Institute Clinical Neuroscience Institute, London, UK.
¹⁷ NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
¹⁸ Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
¹⁹ Department of Neurology, Skåne University Hospital, Lund, Sweden.
²⁰ Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden. oskar.hansson@med.lu.se.

^# Contributed equally.

Abstract

Blood-based biomarkers for screening may guide tau positrion emissition tomography (PET) scan referrals to optimize prognostic evaluation in Alzheimer's disease. Plasma Aβ42/Aβ40, pTau181, pTau217, pTau231, NfL, and GFAP were measured along with tau-PET in memory clinic patients with subjective cognitive decline, mild cognitive impairment or dementia, in the Swedish BioFINDER-2 study (n = 548) and in the TRIAD study (n = 179). For each plasma biomarker, cutoffs were determined for 90%, 95%, or 97.5% sensitivity to detect tau-PET-positivity. We calculated the percentage of patients below the cutoffs (who would not undergo tau-PET; "saved scans") and the tau-PET-positivity rate among participants above the cutoffs (who would undergo tau-PET; "positive predictive value"). Generally, plasma pTau217 performed best. At the 95% sensitivity cutoff in both cohorts, pTau217 resulted in avoiding nearly half tau-PET scans, with a tau-PET-positivity rate among those who would be referred for a scan around 70%. And although tau-PET was strongly associated with subsequent cognitive decline, in BioFINDER-2 it predicted cognitive decline only among individuals above the referral cutoff on plasma pTau217, supporting that this workflow could reduce prognostically uninformative tau-PET scans. In conclusion, plasma pTau217 may guide selection of patients for tau-PET, when accurate prognostic information is of clinical value.

MeSH terms

Alzheimer Disease* / diagnostic imaging
Amyloid beta-Peptides
Biomarkers
Cognitive Dysfunction* / diagnostic imaging
Humans
Positron-Emission Tomography
Workflow
tau Proteins

Substances

Amyloid beta-Peptides
tau Proteins
Biomarkers

Abstract

MeSH terms

Substances

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