Plasma p-tau212 antemortem diagnostic performance and prediction of autopsy verification of Alzheimer's disease neuropathology

Przemysław R Kac; Fernando González-Ortiz; Andreja Emeršič; Maciej Dulewicz; Srinivas Koutarapu; Michael Turton; Yang An; Denis Smirnov; Agnieszka Kulczyńska-Przybik; Vijay R Varma; Nicholas J Ashton; Laia Montoliu-Gaya; Elena Camporesi; Izabela Winkel; Bogusław Paradowski; Abhay Moghekar; Juan C Troncoso; Tammaryn Lashley; Gunnar Brinkmalm; Susan M Resnick; Barbara Mroczko; Hlin Kvartsberg; Milica Gregorič Kramberger; Jörg Hanrieder; Saša Čučnik; Peter Harrison; Henrik Zetterberg; Piotr Lewczuk; Madhav Thambisetty; Uroš Rot; Douglas Galasko; Kaj Blennow; Thomas K Karikari

doi:10.1038/s41467-024-46876-7

Plasma p-tau212 antemortem diagnostic performance and prediction of autopsy verification of Alzheimer's disease neuropathology

Nat Commun. 2024 Mar 23;15(1):2615. doi: 10.1038/s41467-024-46876-7.

Authors

Przemysław R Kac¹, Fernando González-Ortiz^{2

3}, Andreja Emeršič^{4

5}, Maciej Dulewicz², Srinivas Koutarapu², Michael Turton⁶, Yang An⁷, Denis Smirnov⁸, Agnieszka Kulczyńska-Przybik⁹, Vijay R Varma¹⁰, Nicholas J Ashton^{2

11

12

13}, Laia Montoliu-Gaya², Elena Camporesi², Izabela Winkel¹⁴, Bogusław Paradowski¹⁵, Abhay Moghekar¹⁶, Juan C Troncoso^{16

17}, Tammaryn Lashley¹⁸, Gunnar Brinkmalm², Susan M Resnick¹⁹, Barbara Mroczko⁹, Hlin Kvartsberg^{2

3}, Milica Gregorič Kramberger^{4

20

21}, Jörg Hanrieder^{2

22}, Saša Čučnik^{4

5

23}, Peter Harrison⁶, Henrik Zetterberg^{2

3

22

24

25

26}, Piotr Lewczuk^{9

27}, Madhav Thambisetty¹⁰, Uroš Rot^{4

20}, Douglas Galasko⁸, Kaj Blennow^{2

3}, Thomas K Karikari^{2

28}

Affiliations

¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, 431 80, Sweden. [email protected].
² Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, 431 80, Sweden.
³ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, 431 80, Sweden.
⁴ Department of Neurology, University Medical Centre Ljubljana, Ljubljana, 1000, Slovenia.
⁵ Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
⁶ Bioventix Plc, Farnham, GU9 7SX, UK.
⁷ Brain Aging and Behavior Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
⁸ Department of Neurosciences, University of California, San Diego, CA, 92161, USA.
⁹ Department of Neurodegeneration Diagnostics, Medical University of Białystok, Białystok, 15-269, Poland.
¹⁰ Clinical and Translational Neuroscience Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
¹¹ Department of Old Age Psychiatry, King's College London, London, SE5 8AF, UK.
¹² Centre for Age-Related Medicine, Stavanger University Hospital, 4011, Stavanger, Norway.
¹³ South London & Maudsley NHS Foundation, NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia, SE5 8AF, London, UK.
¹⁴ Dementia Disorders Center, Medical University of Wrocław, 59-330, Ścinawa, Poland.
¹⁵ Department of Neurology, Medical University of Wrocław, 50-556, Wrocław, Poland.
¹⁶ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
¹⁷ Department of Pathology, John Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
¹⁸ Department of Neurodegenerative diseases, UCL Queen Square Institute of Neurology, WC1N 1PJ, London, UK.
¹⁹ Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
²⁰ Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
²¹ Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, 141 52, Huddinge, Sweden.
²² Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, Queen Square, London, WC1E 6BT, UK.
²³ Department of Rheumatology, University Medical Center Ljubljana, Ljubljana, Slovenia.
²⁴ UK Dementia Research Institute, University College London, London, WC1E 6BT, UK.
²⁵ Hong Kong Center for Neurodegenerative Diseases, HKCeND, Hong Kong, 1512-1518, China.
²⁶ School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, 53726, USA.
²⁷ Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, 91054, Germany.
²⁸ Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA.

Abstract

Blood phosphorylated tau (p-tau) biomarkers, including p-tau217, show high associations with Alzheimer's disease (AD) neuropathologic change and clinical stage. Certain plasma p-tau217 assays recognize tau forms phosphorylated additionally at threonine-212, but the contribution of p-tau212 alone to AD is unknown. We developed a blood-based immunoassay that is specific to p-tau212 without cross-reactivity to p-tau217. Here, we examined the diagnostic utility of plasma p-tau212. In five cohorts (n = 388 participants), plasma p-tau212 showed high performances for AD diagnosis and for the detection of both amyloid and tau pathology, including at autopsy as well as in memory clinic populations. The diagnostic accuracy and fold changes of plasma p-tau212 were similar to those for p-tau217 but higher than p-tau181 and p-tau231. Immunofluorescent staining of brain tissue slices showed prominent p-tau212 reactivity in neurofibrillary tangles that co-localized with p-tau217 and p-tau202/205. These findings support plasma p-tau212 as a peripherally accessible biomarker of AD pathophysiology.

MeSH terms

Alzheimer Disease* / diagnosis
Amyloid beta-Peptides
Autopsy
Biomarkers
Humans
Neurofibrillary Tangles
Neuropathology
Plasma
tau Proteins

Substances

tau Proteins
Biomarkers
Amyloid beta-Peptides

Abstract

MeSH terms

Substances

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