[en] [en] IMPORTANCE: Blood phosphorylated tau (p-tau) and amyloid-β peptides (Aβ) are promising peripheral biomarkers of Alzheimer disease (AD) pathology. However, their potential alterations due to alternative mechanisms, such as hypoxia in patients resuscitated from cardiac arrest, are not known.
OBJECTIVE: To evaluate whether the levels and trajectories of blood p-tau, Aβ42, and Aβ40 following cardiac arrest, in comparison with neural injury markers neurofilament light (NfL) and total tau (t-tau), can be used for neurological prognostication following cardiac arrest.
DESIGN, SETTING, AND PARTICIPANTS: This prospective clinical biobank study used data from the randomized Target Temperature Management After Out-of-Hospital Cardiac Arrest (TTM) trial. Unconscious patients with cardiac arrest of presumed cardiac origin were included between November 11, 2010, and January 10, 2013, from 29 international sites. Serum analysis for serum NfL and t-tau were performed between August 1 and August 23, 2017. Serum p-tau, Aβ42, and Aβ40 were analyzed between July 1 and July 15, 2021, and between May 13 and May 25, 2022. A total of 717 participants from the TTM cohort were examined: an initial discovery subset (n = 80) and a validation subset. Both subsets were evenly distributed for good and poor neurological outcome after cardiac arrest.
EXPOSURES: Serum p-tau, Aβ42, and Aβ40 concentrations using single molecule array technology. Serum levels of NfL and t-tau were included as comparators.
MAIN OUTCOMES AND MEASURES: Blood biomarker levels at 24 hours, 48 hours, and 72 hours after cardiac arrest. Poor neurologic outcome at 6-month follow-up, defined according to the cerebral performance category scale as category 3 (severe cerebral disability), 4 (coma), or 5 (brain death).
RESULTS: This study included 717 participants (137 [19.1%] female and 580 male [80.9%]; mean [SD] age, 63.9 [13.5] years) who experienced out-of-hospital cardiac arrest. Significantly elevated serum p-tau levels were observed at 24 hours, 48 hours, and 72 hours in cardiac arrest patients with poor neurological outcome. The magnitude and prognostication of the change was greater at 24 hours (area under the receiver operating characteristic curve [AUC], 0.96; 95% CI, 0.95-0.97), which was similar to NfL (AUC, 0.94; 95% CI, 0.92-0.96). However, at later time points, p-tau levels decreased and were weakly associated with neurological outcome. In contrast, NfL and t-tau maintained high diagnostic accuracies, even 72 hours after cardiac arrest. Serum Aβ42 and Aβ40 concentrations increased over time in most patients but were only weakly associated with neurological outcome.
CONCLUSIONS AND RELEVANCE: In this case-control study, blood biomarkers indicative of AD pathology demonstrated different dynamics of change after cardiac arrest. The increase of p-tau at 24 hours after cardiac arrest suggests a rapid secretion from the interstitial fluid following hypoxic-ischemic brain injury rather than ongoing neuronal injury like NfL or t-tau. In contrast, delayed increases of Aβ peptides after cardiac arrest indicate activation of amyloidogenic processing in response to ischemia.
Disciplines :
Anesthesia & intensive care
Author, co-author :
Ashton, Nicholas J; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden ; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden ; Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, United Kingdom ; National Institute for Health and Care Research Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia, South London and Maudsley National Health Service Foundation, London, United Kingdom
Moseby-Knappe, Marion; Skåne University Hospital, Department of Clinical Sciences, Neurology, Lund University, Lund, Sweden
Benedet, Andrea L; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
Grötschel, Lana; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
Lantero-Rodriguez, Juan; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
Karikari, Thomas K; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden ; McGill Centre for Studies in Aging, Translational Neuroimaging Laboratory, McGill University, Montreal, Quebec, Canada
Hassager, Christian; Department of Cardiology, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
Wise, Matt P; Adult Critical Care, University Hospital of Wales, Heath Park, Cardiff, United Kingdom
STAMMET, Pascal ; University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) > Medical Education ; Department of Anesthesia and Intensive Care, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg
Kjaergaard, Jesper; Department of Cardiology, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
Friberg, Hans; Department of Clinical Sciences Lund, Anesthesia & Intensive Care Section, Helsingborg Hospital, Lund University, Lund, Sweden
Nielsen, Niklas; Department of Clinical Sciences Lund, Anesthesia & Intensive Care Section, Helsingborg Hospital, Lund University, Lund, Sweden
Cronberg, Tobias; Skåne University Hospital, Department of Clinical Sciences, Neurology, Lund University, Lund, Sweden
Zetterberg, Henrik; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden ; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden ; Department of Neurodegenerative Disease, University College London Queen Square Institute of Neurology, London, United Kingdom ; United Kingdom Dementia Research Institute at University College London, University College London, London, United Kingdom ; Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China
Blennow, Kaj; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden ; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
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