. 2024 Apr;271(4):2053-2066.

doi: 10.1007/s00415-023-12148-5. Epub 2024 Jan 9.

Head-to-head study of diagnostic accuracy of plasma and cerebrospinal fluid p-tau217 versus p-tau181 and p-tau231 in a memory clinic cohort

Augusto J Mendes^{1

2}, Federica Ribaldi^{3

4}, Aurelien Lathuiliere^{3

4}, Nicholas J Ashton^{5

6

7

8}, Shorena Janelidze⁹, Henrik Zetterberg^{5

10

11

12

13

14}, Max Scheffler¹⁵, Frédéric Assal¹⁶, Valentina Garibotto^{17

18

19}, Kaj Blennow^{5

10

20

21}, Oskar Hansson^{9

22}, Giovanni B Frisoni^{3

4}

Affiliations

¹ Laboratory of Neuroimaging of Aging (LANVIE), University of Geneva, Geneva, Switzerland. augusto.martinsmendes@unige.ch.
² Geneva Memory Center, Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland. augusto.martinsmendes@unige.ch.
³ Laboratory of Neuroimaging of Aging (LANVIE), University of Geneva, Geneva, Switzerland.
⁴ Geneva Memory Center, Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland.
⁵ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁶ King's College London, Institute of Psychiatry, Psychology and Neuroscience Maurice Wohl Institute Clinical Neuroscience Institute, London, UK.
⁷ NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
⁸ Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
⁹ Clinical Memory Research Unit, Lund University, 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, UK.
¹³ Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.
¹⁴ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
¹⁵ Division of Radiology, Geneva University Hospitals, Geneva, Switzerland.
¹⁶ Division of Neurology, Department of Clinical Neurosciences, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
¹⁷ Laboratory of Neuroimaging and Innovative Molecular Tracers (NIMTlab), Geneva University Neurocenter and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
¹⁸ Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospitals, Geneva, Switzerland.
¹⁹ CIBM Center for Biomedical Imaging, Geneva, Switzerland.
²⁰ Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.
²¹ Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, People's Republic of China.
²² Memory Clinic, Skåne University Hospital, Malmö, Sweden.

PMID: 38195896
PMCID: PMC10972950
DOI: 10.1007/s00415-023-12148-5

Head-to-head study of diagnostic accuracy of plasma and cerebrospinal fluid p-tau217 versus p-tau181 and p-tau231 in a memory clinic cohort

Augusto J Mendes et al. J Neurol. 2024 Apr.

. 2024 Apr;271(4):2053-2066.

doi: 10.1007/s00415-023-12148-5. Epub 2024 Jan 9.

Authors

Affiliations

¹ Laboratory of Neuroimaging of Aging (LANVIE), University of Geneva, Geneva, Switzerland. augusto.martinsmendes@unige.ch.
² Geneva Memory Center, Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland. augusto.martinsmendes@unige.ch.
³ Laboratory of Neuroimaging of Aging (LANVIE), University of Geneva, Geneva, Switzerland.
⁴ Geneva Memory Center, Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland.
⁵ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁶ King's College London, Institute of Psychiatry, Psychology and Neuroscience Maurice Wohl Institute Clinical Neuroscience Institute, London, UK.
⁷ NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
⁸ Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
⁹ Clinical Memory Research Unit, Lund University, 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, UK.
¹³ Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.
¹⁴ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
¹⁵ Division of Radiology, Geneva University Hospitals, Geneva, Switzerland.
¹⁶ Division of Neurology, Department of Clinical Neurosciences, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
¹⁷ Laboratory of Neuroimaging and Innovative Molecular Tracers (NIMTlab), Geneva University Neurocenter and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
¹⁸ Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospitals, Geneva, Switzerland.
¹⁹ CIBM Center for Biomedical Imaging, Geneva, Switzerland.
²⁰ Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.
²¹ Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, People's Republic of China.
²² Memory Clinic, Skåne University Hospital, Malmö, Sweden.

PMID: 38195896
PMCID: PMC10972950
DOI: 10.1007/s00415-023-12148-5

Abstract

Background and objective: Phosphorylated tau (p-tau) 217 has recently received attention because it seems more reliable than other p-tau variants for identifying Alzheimer's disease (AD) pathology. Thus, we aimed to compare the diagnostic accuracy of plasma and CSF p-tau217 with p-tau181 and p-tau231 in a memory clinic cohort.

Methods: The study included 114 participants (CU = 33; MCI = 67; Dementia = 14). The p-tau variants were correlated versus continuous measures of amyloid (A) and tau (T)-PET. The p-tau phospho-epitopes were assessed through: (i) effect sizes (δ) between diagnostic and A ± and T ± groups; (ii) receiver operating characteristic (ROC) analyses in A-PET and T-PET.

Results: The correlations between both plasma and CSF p-tau217 with A-PET and T-PET (r range 0.64-0.83) were stronger than those of p-tau181 (r range 0.44-0.79) and p-tau231 (r range 0.46-0.76). Plasma p-tau217 showed significantly higher diagnostic accuracy than p-tau181 and p-tau231 in (i) differences between diagnostic and biomarker groups (δ_range: p-tau217 = 0.55-0.96; p-tau181 = 0.51-0.67; p-tau231 = 0.53-0.71); (ii) ROC curves to identify A-PET and T-PET positivity (AUC_average: p-tau217 = 0.96; p-tau181 = 0.76; p-tau231 = 0.79). On the other hand, CSF p-tau217 (AUC_average = 0.95) did not reveal significant differences in A-PET and T-PET AUC than p-tau181 (AUC_average = 0.88) and p-tau231 (AUC_average = 0.89).

Discussion: Plasma p-tau217 demonstrated better performance in the identification of AD pathology and clinical phenotypes in comparison with other variants of p-tau in a memory clinic cohort. Furthermore, p-tau217 had comparable performance in plasma and CSF. Our findings suggest the potential of plasma p-tau217 in the diagnosis and screening for AD, which could allow for a decreased use of invasive biomarkers in the future.

Keywords: p-tau; Alzheimer’s disease; Amyloid; CSF; Plasma; Tau.

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Conflict of interest statement

GBF has received unrestricted grants and support for event organization from ROCHE Pharmaceuticals; OM Pharma; EISAI Pharmaceuticals; Biogen Pharmaceuticals. VG received grants and speaker fees through her institution from Siemens Healthineers, GE Healthcare, Novo Nordisk and Janssen. HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). OH has acquired research support (for the institution) from ADx, AVID Radiopharmaceuticals, Biogen, Eli Lilly, Eisai, Fujirebio, GE Healthcare, Pfizer, and Roche. In the past 2 years, he has received consultancy/speaker fees from AC Immune, Amylyx, Alzpath, BioArctic, Biogen, Cerveau, Eisai, Eli Lilly, Fujirebio, Merck, Novartis, Novo Nordisk, Roche, Sanofi and Siemens. The other authors have nothing to disclose.

Figures

**Fig. 1**
Scatter plots between ATN-C measures and p-tau variants measured in plasma and CSF

**Fig. 2**
Scatter plots among the different forms of p-tau in plasma and CSF

**Fig. 3**
Box plots of plasma and CSF p-tau217, p-tau181, and p-tau231 by cognitive severity. **p < 0.01; *p < 0.05

**Fig. 4**
Box plots of plasma and CSF p-tau217, p-tau181, and p-tau231 according to the positivity in amyloid and tau-PET. ***p < 0.001; **p < 0.01; *p < 0.05; + < 0.1

**Fig. 5**
Classification accuracy of the three variants of p-tau measured in plasma and CSF in amyloid and tau positivity evaluated in PET

**Fig. 6**
Violin plots for the three p-tau variants evaluated in plasma with the 95% sensitivity, 95% specificity, and optimal cut-off over the amyloid and tau status assessed in PET

See this image and copyright information in PMC

References

1. Jack CR, Bennett DA, Blennow K, et al. A/T/N: an unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology. 2016;87:539–547. doi: 10.1212/WNL.0000000000002923. - DOI - PMC - PubMed
1. Gonzalez-Ortiz F, Kac PR, Brum WS, et al. Plasma phospho-tau in Alzheimer’s disease: towards diagnostic and therapeutic trial applications. Mol Neurodegener. 2023 doi: 10.1186/S13024-023-00605-8. - DOI - PMC - PubMed
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Head-to-head study of diagnostic accuracy of plasma and cerebrospinal fluid p-tau217 versus p-tau181 and p-tau231 in a memory clinic cohort

Affiliations

Head-to-head study of diagnostic accuracy of plasma and cerebrospinal fluid p-tau217 versus p-tau181 and p-tau231 in a memory clinic cohort

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical