Spontaneous and perturbation-based EEG cortical excitability markers are associated with plasma p-tau181 concentration in healthy middle-aged adults

In early-stage Alzheimer's disease (AD) amyloid-β (Aβ) deposition can induce neuronal hyperactivity, thereby potentially triggering activity-dependent neuronal secretion of phosphorylated tau (p-tau), ensuing tau aggregation and spread. Therefore, cortical excitability is a candidate biomarker...

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Main Authors: Ruben Perellón-Alfonso, Kilian Abellaneda-Pérez, Indre Pileckyte, María Cabello-Toscano, Lídia Mulet-Pons, Lídia Vaqué-Alcázar, Gabriele Cattaneo, María Redondo-Camós, Goretti España-Irla, Selma Delgado-Gallen, Javier Solana Sánchez, Henrik Zetterberg, Jose M. Tormos, Nicolai Franzmeier, Alvaro Pascual-Leone, David Bartrés-Faz
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Heliyon
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405844024171496
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author Ruben Perellón-Alfonso
Kilian Abellaneda-Pérez
Indre Pileckyte
María Cabello-Toscano
Lídia Mulet-Pons
Lídia Vaqué-Alcázar
Gabriele Cattaneo
María Redondo-Camós
Goretti España-Irla
Selma Delgado-Gallen
Javier Solana Sánchez
Henrik Zetterberg
Jose M. Tormos
Nicolai Franzmeier
Alvaro Pascual-Leone
David Bartrés-Faz
author_facet Ruben Perellón-Alfonso
Kilian Abellaneda-Pérez
Indre Pileckyte
María Cabello-Toscano
Lídia Mulet-Pons
Lídia Vaqué-Alcázar
Gabriele Cattaneo
María Redondo-Camós
Goretti España-Irla
Selma Delgado-Gallen
Javier Solana Sánchez
Henrik Zetterberg
Jose M. Tormos
Nicolai Franzmeier
Alvaro Pascual-Leone
David Bartrés-Faz
author_sort Ruben Perellón-Alfonso
collection DOAJ
description In early-stage Alzheimer's disease (AD) amyloid-β (Aβ) deposition can induce neuronal hyperactivity, thereby potentially triggering activity-dependent neuronal secretion of phosphorylated tau (p-tau), ensuing tau aggregation and spread. Therefore, cortical excitability is a candidate biomarker for early AD detection. Moreover, lowering neuronal excitability could potentially complement strategies to reduce Aβ and tau buildup. There is, however, a lack of understanding of the relationship between cortical excitability and p-tau increase in vivo. Therefore, in a sample of 658 healthy middle-aged (between the ages of 40 and 65) participants of the Barcelona Brain Health Initiative cohort study, we examined the relation of blood-based tau, phosphorylated at amino acid 181 (p-tau181), reflecting neuronal p-tau secretion; neurofilament light chain (NfL), as a passively released control for p-tau181; and electroencephalography (EEG) markers of cortical excitability. A subsample of 47 participants also completed a controlled brain perturbation approach via transcranial magnetic stimulation (TMS) with concurrent EEG. Results show that both spontaneous (i.e., resting-state) and perturbation-based TMS-EEG markers, are associated with blood p-tau181, particularly in older individuals. The perturbation-based marker was a significantly more sensitive predictor of p-tau181 concentration than the spontaneous resting state EEG-based marker. The relationships observed are not present for the NfL control. These results show that relationships between p-tau181 and cortical excitability are present in healthy middle-aged subjects and that p-tau181 increases may reflect activity-dependent secretion.
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spelling doaj-art-10a79316cd954ff08fcd954c4cf39c1c2025-08-20T01:58:28ZengElsevierHeliyon2405-84402024-12-011024e4111810.1016/j.heliyon.2024.e41118Spontaneous and perturbation-based EEG cortical excitability markers are associated with plasma p-tau181 concentration in healthy middle-aged adultsRuben Perellón-Alfonso0Kilian Abellaneda-Pérez1Indre Pileckyte2María Cabello-Toscano3Lídia Mulet-Pons4Lídia Vaqué-Alcázar5Gabriele Cattaneo6María Redondo-Camós7Goretti España-Irla8Selma Delgado-Gallen9Javier Solana Sánchez10Henrik Zetterberg11Jose M. Tormos12Nicolai Franzmeier13Alvaro Pascual-Leone14David Bartrés-Faz15Department of Medicine, Faculty of Medicine and Health Sciences, and Institute of Neurosciences, University of Barcelona, Barcelona, Spain; Institut d‘Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la Universitat Autònoma de Barcelona, Barcelona, Spain; Corresponding author. Department of Medicine, Faculty of Medicine and Health Sciences, and Institute of Neurosciences, University of Barcelona, Barcelona, Spain.Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la Universitat Autònoma de Barcelona, Barcelona, Spain; Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain; Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, SpainCenter for Brain and Cognition, Pompeu Fabra University, Barcelona, SpainDepartment of Medicine, Faculty of Medicine and Health Sciences, and Institute of Neurosciences, University of Barcelona, Barcelona, Spain; Institut d‘Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, SpainDepartment of Medicine, Faculty of Medicine and Health Sciences, and Institute of Neurosciences, University of Barcelona, Barcelona, Spain; Institut d‘Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, SpainDepartment of Medicine, Faculty of Medicine and Health Sciences, and Institute of Neurosciences, University of Barcelona, Barcelona, Spain; Institut d‘Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Sant Pau Memory Unit, Department of Neurology, Institut d’Investigacions Biomèdiques Sant Pau-Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainInstitut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la Universitat Autònoma de Barcelona, Barcelona, Spain; Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain; Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, SpainInstitut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la Universitat Autònoma de Barcelona, Barcelona, Spain; Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain; Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, SpainDepartment of Psychology, Northeastern University, Boston, MA, USA; Center for Cognitive & Brain Health, Northeastern University, Boston, MA, USA; Department of Physical Therapy, Movement, & Rehabilitation Sciences, Northeastern University, Boston, MA, USAInstitut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la Universitat Autònoma de Barcelona, Barcelona, Spain; Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain; Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, SpainInstitut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la Universitat Autònoma de Barcelona, Barcelona, Spain; Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain; Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, SpainDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK; UK Dementia Research Institute at UCL, London, UK; Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USACentro de Investigación Translacional San Alberto Magno - Facultad Ciencias de la Salud - Universidad Católica de Valencia, SpainInstitute for Stroke and Dementia Research (ISD), University Hospital, LMU, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany; University of Gothenburg, The Sahlgrenska Academy, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, SwedenHinda and Arthur Marcus Institute for Aging Research and Deanna and Sidney Wolk Center for Memory Health, Hebrew SeniorLife, Boston, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA; Linus Health, Inc., Boston, MA, USADepartment of Medicine, Faculty of Medicine and Health Sciences, and Institute of Neurosciences, University of Barcelona, Barcelona, Spain; Institut d‘Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la Universitat Autònoma de Barcelona, Barcelona, Spain; Corresponding author. Department of Medicine, Faculty of Medicine and Health Sciences, and Institute of Neurosciences, University of Barcelona, Barcelona, SpainIn early-stage Alzheimer's disease (AD) amyloid-β (Aβ) deposition can induce neuronal hyperactivity, thereby potentially triggering activity-dependent neuronal secretion of phosphorylated tau (p-tau), ensuing tau aggregation and spread. Therefore, cortical excitability is a candidate biomarker for early AD detection. Moreover, lowering neuronal excitability could potentially complement strategies to reduce Aβ and tau buildup. There is, however, a lack of understanding of the relationship between cortical excitability and p-tau increase in vivo. Therefore, in a sample of 658 healthy middle-aged (between the ages of 40 and 65) participants of the Barcelona Brain Health Initiative cohort study, we examined the relation of blood-based tau, phosphorylated at amino acid 181 (p-tau181), reflecting neuronal p-tau secretion; neurofilament light chain (NfL), as a passively released control for p-tau181; and electroencephalography (EEG) markers of cortical excitability. A subsample of 47 participants also completed a controlled brain perturbation approach via transcranial magnetic stimulation (TMS) with concurrent EEG. Results show that both spontaneous (i.e., resting-state) and perturbation-based TMS-EEG markers, are associated with blood p-tau181, particularly in older individuals. The perturbation-based marker was a significantly more sensitive predictor of p-tau181 concentration than the spontaneous resting state EEG-based marker. The relationships observed are not present for the NfL control. These results show that relationships between p-tau181 and cortical excitability are present in healthy middle-aged subjects and that p-tau181 increases may reflect activity-dependent secretion.http://www.sciencedirect.com/science/article/pii/S2405844024171496Alzheimer's diseaseTauEEGTranscranial magnetic stimulation
spellingShingle Ruben Perellón-Alfonso
Kilian Abellaneda-Pérez
Indre Pileckyte
María Cabello-Toscano
Lídia Mulet-Pons
Lídia Vaqué-Alcázar
Gabriele Cattaneo
María Redondo-Camós
Goretti España-Irla
Selma Delgado-Gallen
Javier Solana Sánchez
Henrik Zetterberg
Jose M. Tormos
Nicolai Franzmeier
Alvaro Pascual-Leone
David Bartrés-Faz
Spontaneous and perturbation-based EEG cortical excitability markers are associated with plasma p-tau181 concentration in healthy middle-aged adults
Heliyon
Alzheimer's disease
Tau
EEG
Transcranial magnetic stimulation
title Spontaneous and perturbation-based EEG cortical excitability markers are associated with plasma p-tau181 concentration in healthy middle-aged adults
title_full Spontaneous and perturbation-based EEG cortical excitability markers are associated with plasma p-tau181 concentration in healthy middle-aged adults
title_fullStr Spontaneous and perturbation-based EEG cortical excitability markers are associated with plasma p-tau181 concentration in healthy middle-aged adults
title_full_unstemmed Spontaneous and perturbation-based EEG cortical excitability markers are associated with plasma p-tau181 concentration in healthy middle-aged adults
title_short Spontaneous and perturbation-based EEG cortical excitability markers are associated with plasma p-tau181 concentration in healthy middle-aged adults
title_sort spontaneous and perturbation based eeg cortical excitability markers are associated with plasma p tau181 concentration in healthy middle aged adults
topic Alzheimer's disease
Tau
EEG
Transcranial magnetic stimulation
url http://www.sciencedirect.com/science/article/pii/S2405844024171496
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