Comparing tau status determined via plasma pTau181, pTau231 and [¹⁸F]MK6240 tau-PET

Cécile Tissot¹, Joseph Therriault¹, Peter Kunach¹, Andréa L Benedet², Tharick A Pascoal³, Nicholas J Ashton⁴, Thomas K Karikari⁵, Stijn Servaes¹, Firoza Z Lussier¹, Mira Chamoun¹, Dana L Tudorascu⁶, Jenna Stevenson¹, Nesrine Rahmouni¹, Nina Margherita Poltronetti¹, Vanessa Pallen¹, Gleb Bezgin¹, Min Su Kang¹, Sulantha S Mathotaarachchi¹, Yi-Ting Wang¹, Jaime Fernandez Arias¹, Pamela Cristina Lukasewicz Ferreira⁶, João Pedro Ferrari-Souza⁷, Eugeen Vanmechelen⁸, Kaj Blennow⁹, Henrik Zetterberg¹⁰, Serge Gauthier¹¹, Pedro Rosa-Neto¹²

Affiliations

¹ McGill University, Montreal, QC, Canada; McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, 6875 La Salle Blvd - FBC room 3149, Verdun, QC H4H 1R3, Canada; Translational Neuroimaging Laboratory, Alzheimer's Disease Research Unit, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, McGill University Research Centre for Studies in Aging, Douglas Research Institute, Montreal, Canada.
² McGill University, Montreal, QC, Canada; McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, 6875 La Salle Blvd - FBC room 3149, Verdun, QC H4H 1R3, Canada; Translational Neuroimaging Laboratory, Alzheimer's Disease Research Unit, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, McGill University Research Centre for Studies in Aging, Douglas Research Institute, Montreal, Canada; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Sweden.
³ McGill University, Montreal, QC, Canada; McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, 6875 La Salle Blvd - FBC room 3149, Verdun, QC H4H 1R3, Canada; Translational Neuroimaging Laboratory, Alzheimer's Disease Research Unit, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, McGill University Research Centre for Studies in Aging, Douglas Research Institute, Montreal, Canada; University of Pittsburgh, Pittsburgh, PA, USA.
⁴ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Sweden; King's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London, UK; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
⁵ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Sweden; University of Pittsburgh, Pittsburgh, PA, USA.
⁶ University of Pittsburgh, Pittsburgh, PA, USA.
⁷ University of Pittsburgh, Pittsburgh, PA, USA; Graduate program in Biological Sciences, Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
⁸ ADx NeuroSciences, Ghent, Belgium.
⁹ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; UK Dementia Research Institute at UCL, London, United Kingdom.
¹⁰ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Sweden; UK Dementia Research Institute at UCL, London, United Kingdom; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom.
¹¹ McGill University, Montreal, QC, Canada; McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, 6875 La Salle Blvd - FBC room 3149, Verdun, QC H4H 1R3, Canada; Douglas Hospital Research Centre, Verdun, QC, Canada.
¹² McGill University, Montreal, QC, Canada; McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, 6875 La Salle Blvd - FBC room 3149, Verdun, QC H4H 1R3, Canada; Translational Neuroimaging Laboratory, Alzheimer's Disease Research Unit, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, McGill University Research Centre for Studies in Aging, Douglas Research Institute, Montreal, Canada. Electronic address: pedro.rosa@mcgill.ca.

PMID: 35134647
PMCID: PMC8844756
DOI: 10.1016/j.ebiom.2022.103837

Comparing tau status determined via plasma pTau181, pTau231 and [¹⁸F]MK6240 tau-PET

Cécile Tissot et al. EBioMedicine. 2022 Feb.

. 2022 Feb:76:103837.

doi: 10.1016/j.ebiom.2022.103837. Epub 2022 Feb 6.

Authors

Affiliations

¹ McGill University, Montreal, QC, Canada; McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, 6875 La Salle Blvd - FBC room 3149, Verdun, QC H4H 1R3, Canada; Translational Neuroimaging Laboratory, Alzheimer's Disease Research Unit, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, McGill University Research Centre for Studies in Aging, Douglas Research Institute, Montreal, Canada.
² McGill University, Montreal, QC, Canada; McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, 6875 La Salle Blvd - FBC room 3149, Verdun, QC H4H 1R3, Canada; Translational Neuroimaging Laboratory, Alzheimer's Disease Research Unit, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, McGill University Research Centre for Studies in Aging, Douglas Research Institute, Montreal, Canada; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Sweden.
³ McGill University, Montreal, QC, Canada; McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, 6875 La Salle Blvd - FBC room 3149, Verdun, QC H4H 1R3, Canada; Translational Neuroimaging Laboratory, Alzheimer's Disease Research Unit, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, McGill University Research Centre for Studies in Aging, Douglas Research Institute, Montreal, Canada; University of Pittsburgh, Pittsburgh, PA, USA.
⁴ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Sweden; King's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London, UK; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
⁵ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Sweden; University of Pittsburgh, Pittsburgh, PA, USA.
⁶ University of Pittsburgh, Pittsburgh, PA, USA.
⁷ University of Pittsburgh, Pittsburgh, PA, USA; Graduate program in Biological Sciences, Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
⁸ ADx NeuroSciences, Ghent, Belgium.
⁹ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; UK Dementia Research Institute at UCL, London, United Kingdom.
¹⁰ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Sweden; UK Dementia Research Institute at UCL, London, United Kingdom; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom.
¹¹ McGill University, Montreal, QC, Canada; McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, 6875 La Salle Blvd - FBC room 3149, Verdun, QC H4H 1R3, Canada; Douglas Hospital Research Centre, Verdun, QC, Canada.
¹² McGill University, Montreal, QC, Canada; McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, 6875 La Salle Blvd - FBC room 3149, Verdun, QC H4H 1R3, Canada; Translational Neuroimaging Laboratory, Alzheimer's Disease Research Unit, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, McGill University Research Centre for Studies in Aging, Douglas Research Institute, Montreal, Canada. Electronic address: pedro.rosa@mcgill.ca.

PMID: 35134647
PMCID: PMC8844756
DOI: 10.1016/j.ebiom.2022.103837

Abstract

Background: Tau in Alzheimer's disease (AD) is assessed via cerebrospinal fluid (CSF) and Positron emission tomography (PET). Novel methods to detect phosphorylated tau (pTau) in blood have been recently developed. We aim to investigate agreement of tau status as determined by [¹⁸F]MK6240 tau-PET, plasma pTau181 and pTau231.

Methods: We assessed cognitively unimpaired young, cognitively unimpaired, mild cognitive impairment and AD individuals with [¹⁸F]MK6240, plasma pTau181, pTau 231, [¹⁸F]AZD4694 amyloid-PET and MRI. A subset underwent CSF assessment. We conducted ROC curves to obtain cut-off values for plasma pTau epitopes. Individuals were categorized as positive or negative in all biomarkers. We then compared the distribution among concordant and discordant groups in relation to diagnosis, Aβ status, APOEε4 status, [¹⁸F]AZD4694 global SUVR, hippocampal volume and CSF pTau181.

Findings: The threshold for positivity was 15.085 pg/mL for plasma pTau181 and 17.652 pg/mL for plasma pTau231. Most individuals had concordant statuses, however, 18% of plasma181/PET, 26% of plasma231/PET and 25% of the pTau231/pTau181 were discordant. Positivity to at least one biomarker was often accompanied by diagnosis of cognitive impairment, Aβ positivity, APOEε4 carriership, higher levels of [¹⁸F]AZD4694 global SUVR, hippocampal atrophy and CSF pTau181.

Interpretation: Plasma pTau181, pTau231 and [¹⁸F]MK6240 seem to reflect different stages of tau progression. Plasma biomarkers can be useful in the context of diagnostic information and clinical trials, to evaluate the disease stage. Moreover, they seem to confidently evaluate tau-PET positivity.

Funding: Moreover, this study was supported by Weston Brain Institute, Canadian Institute of Health Research and Fonds de Recherche du Québec.

Keywords: Alzheimer's disease; Plasma; Positron emission tomography; Tau.

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Conflict of interest statement

Declaration of interests Nothing to disclose.

Figures

**Figure 1**
Correlation plots (n = 254). a. Correlation between plasma pTau181 and [¹⁸F]MK6240 temporal meta-ROI SUVR (R = 0.48, p < 0.001), stratified by status and diagnosis. b. Correlation between plasma pTau231 and [¹⁸F]MK6240 temporal meta-ROI SUVR (R = 0.49, p < 0.001) stratified by status and diagnosis. c. Correlation between plasma pTau231 and pTau181 (R = 0.60, p < 0.001) stratified by status and diagnosis.

Figure 2. — **Figure 2**
Demographic information in relation to plasma/PET statuses (n = 254). a. Diagnosis in plasma181/PET b. Diagnosis in plasma231/PET c. Diagnosis in plasma pTau231/pTau181 d. Diagnosis and Aβ status in plasma181/PET e. Diagnosis and Aβ status in plasma231/PET f. Diagnosis and Aβ status in plasma pTau231/pTau181 g. *APOE*ε4 status in plasma181/PET and h. *APOE*ε4 status in plasma231/PET. i. *APOE*ε4 status in plasma pTau231/pTau181.

Figure 3. — **Figure 3**
Alzheimer's disease biomarkers in relation to plasma/PET statuses (n = 254). a. Aβ status in plasma181/PET b. Aβ status in plasma231/PET c. Aβ status in plasma pTau231/pTau181. d. [¹⁸F]AZD4694 global SUVR in plasma181/PET e. [¹⁸F]AZD4694 global SUVR in plasma231/PET f. [¹⁸F]AZD4694 global SUVR in plasma pTau231/pTau181 g. Hippocampal volume in plasma181/PET h. Hippocampal volume in plasma231/PET i. Hippocampal volume in plasma pTau231/pTau181 j. CSF pTau181 levels in plasma181/PET k. CSF pTau181 levels in plasma231/PET l. CSF pTau181 levels in plasma pTau231/pTau181.

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Comparing tau status determined via plasma pTau181, pTau231 and [¹⁸F]MK6240 tau-PET

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Comparing tau status determined via plasma pTau181, pTau231 and [¹⁸F]MK6240 tau-PET

Authors

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Abstract

Conflict of interest statement

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