Spontaneous and perturbation-based EEG cortical excitability markers are associated with plasma p-tau181 concentration in healthy middle-aged adults
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
Affiliations
Ruben Perellón-Alfonso
Department 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.
Kilian Abellaneda-Pérez
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, Spain
Indre Pileckyte
Center for Brain and Cognition, Pompeu Fabra University, Barcelona, Spain
María Cabello-Toscano
Department 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
Lídia Mulet-Pons
Department 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
Lídia Vaqué-Alcázar
Department 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, Spain
Gabriele Cattaneo
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, Spain
María Redondo-Camós
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, Spain
Goretti España-Irla
Department 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, USA
Selma Delgado-Gallen
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, Spain
Javier Solana Sánchez
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, Spain
Henrik Zetterberg
Department 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, USA
Jose M. Tormos
Centro de Investigación Translacional San Alberto Magno - Facultad Ciencias de la Salud - Universidad Católica de Valencia, Spain
Nicolai Franzmeier
Institute 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, Sweden
Alvaro Pascual-Leone
Hinda 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, USA
David Bartrés-Faz
Department 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
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.
