Plasma p-tau231, p-tau181, PET Biomarkers, and Cognitive Change in Older Adults

Pierre-François Meyer^#¹, Nicholas J Ashton^#^{2

3

4

5}, Thomas K Karikari^{2

5}, Cherie Strikwerda-Brown¹, Theresa Köbe¹, Julie Gonneaud¹, Alexa Pichet Binette^{1

6

7}, Hazal Ozlen¹, Yara Yakoub¹, Joel Simrén^{2

8}, Josef Pannee^{2

8}, Juan Lantero-Rodriguez², Anne Labonté¹, Suzanne L Baker⁹, Michael Schöll³, Eugeen Vanmechelen¹⁰, John C S Breitner^{1

6

7}, Henrik Zetterberg^{2

8

11

12}, Kaj Blennow^{2

8}, Judes Poirier^{1

6}, Sylvia Villeneuve^{1

6

7

13}; Presymptomatic Evaluation of Experimental or Novel Treatments for Alzheimer Disease (PREVENT-AD) Research Group

Affiliations

¹ Douglas Mental Health University Institute, Centre for Studies on Prevention of Alzheimer's Disease (StoP-AD), Montreal, Quebec, Canada.
² Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
³ Wallenberg Centre for Molecular and Translational Medicine, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
⁴ King's College London, Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London, UK.
⁵ NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK.
⁶ Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
⁷ McGill Centre for Integrative Neuroscience, McGill University, Montreal, Quebec, Canada.
⁸ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁹ Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA.
¹⁰ ADx NeuroSciences, Ghent, Belgium.
¹¹ Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
¹² UK Dementia Research Institute at UCL, London, UK.
¹³ Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.

^# Contributed equally.

PMID: 35084051
DOI: 10.1002/ana.26308

Plasma p-tau231, p-tau181, PET Biomarkers, and Cognitive Change in Older Adults

Pierre-François Meyer et al. Ann Neurol. 2022 Apr.

. 2022 Apr;91(4):548-560.

doi: 10.1002/ana.26308. Epub 2022 Feb 18.

Authors

Affiliations

¹ Douglas Mental Health University Institute, Centre for Studies on Prevention of Alzheimer's Disease (StoP-AD), Montreal, Quebec, Canada.
² Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
³ Wallenberg Centre for Molecular and Translational Medicine, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
⁴ King's College London, Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London, UK.
⁵ NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK.
⁶ Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
⁷ McGill Centre for Integrative Neuroscience, McGill University, Montreal, Quebec, Canada.
⁸ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁹ Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA.
¹⁰ ADx NeuroSciences, Ghent, Belgium.
¹¹ Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
¹² UK Dementia Research Institute at UCL, London, UK.
¹³ Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.

^# Contributed equally.

PMID: 35084051
DOI: 10.1002/ana.26308

Abstract

Objective: The objective of this study was to evaluate novel plasma p-tau231 and p-tau181, as well as Aβ₄₀ and Aβ₄₂ assays as indicators of tau and Aβ pathologies measured with positron emission tomography (PET), and their association with cognitive change, in cognitively unimpaired older adults.

Methods: In a cohort of 244 older adults at risk of Alzheimer's disease (AD) owing to a family history of AD dementia, we measured single molecule array (Simoa)-based plasma tau biomarkers (p-tau231 and p-tau181), Aβ₄₀ and Aβ₄₂ with immunoprecipitation mass spectrometry, and Simoa neurofilament light (NfL). A subset of 129 participants underwent amyloid-β (¹⁸ F-NAV4694) and tau (¹⁸ F-flortaucipir) PET assessments. We investigated plasma biomarker associations with Aβ and tau PET at the global and voxel level and tested plasma biomarker combinations for improved detection of Aβ-PET positivity. We also investigated associations with 8-year cognitive change.

Results: Plasma p-tau biomarkers correlated with flortaucipir binding in medial temporal, parietal, and inferior temporal regions. P-tau231 showed further associations in lateral parietal and occipital cortices. Plasma Aβ_42/40 explained more variance in global Aβ-PET binding than Aβ₄₂ alone. P-tau231 also showed strong and widespread associations with cortical Aβ-PET binding. Combining Aβ_42/40 with p-tau231 or p-tau181 allowed for good distinction between Aβ-negative and -positive participants (area under the receiver operating characteristic curve [AUC] range = 0.81-0.86). Individuals with low plasma Aβ_42/40 and high p-tau experienced faster cognitive decline.

Interpretation: Plasma p-tau231 showed more robust associations with PET biomarkers than p-tau181 in presymptomatic individuals. The combination of p-tau and Aβ_42/40 biomarkers detected early AD pathology and cognitive decline. Such markers could be used as prescreening tools to reduce the cost of prevention trials. ANN NEUROL 2022;91:548-560.

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References

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Plasma p-tau231, p-tau181, PET Biomarkers, and Cognitive Change in Older Adults

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Plasma p-tau231, p-tau181, PET Biomarkers, and Cognitive Change in Older Adults

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