Personalized whole-brain neural mass models reveal combined Aβ and tau hyperexcitable influences in Alzheimer's disease.

Sanchez-Rodriguez, Lazaro M; Bezgin, Gleb; Carbonell, Felix; Therriault, Joseph; Fernandez-Arias, Jaime; Servaes, Stijn; Rahmouni, Nesrine; Tissot, Cécile; Stevenson, Jenna; Karikari, Thomas K; Ashton, Nicholas J; Benedet, Andréa L; Zetterberg, Henrik; Blennow, Kaj; Triana-Baltzer, Gallen; Kolb, Hartmuth C; Rosa-Neto, Pedro; Iturria-Medina, Yasser

doi:10.1038/s42003-024-06217-2

Title: Personalized whole-brain neural mass models reveal combined Aβ and tau hyperexcitable influences in Alzheimer's disease.

Journal Article · 03 May 2024 · Communications Biology

DOI: https://doi.org/10.1038/s42003-024-06217-2 · OSTI ID:2396865

Sanchez-Rodriguez, Lazaro M ^[1]; Bezgin, Gleb ^[1]; Carbonell, Felix ^[2]; Therriault, Joseph ^[3]; Fernandez-Arias, Jaime ^[3]; Servaes, Stijn ^[3]; Rahmouni, Nesrine ^[3]; Tissot, Cécile ^[4]; Stevenson, Jenna ^[3]; Karikari, Thomas K ^[5]; Ashton, Nicholas J ^[6]; Benedet, Andréa L ^[7]; Zetterberg, Henrik ^[8]; Blennow, Kaj ^[9]; Triana-Baltzer, Gallen ^[10]; Kolb, Hartmuth C ^[10]; Rosa-Neto, Pedro ^[11]; Iturria-Medina, Yasser ^[1]

McGill Univ., Montreal, QC (Canada); Montreal Neurological Institute, Montreal, QC (Canada). McConnell Brain Imaging Centre; Ludmer Centre for Neuroinformatics & Mental Health, Montreal, QC (Canada)
Biospective Inc., Montreal, QC (Canada)
McGill Univ., Montreal, QC (Canada); Montreal Neurological Institute, Montreal, QC (Canada). McConnell Brain Imaging Centre
McGill Univ., Montreal, QC (Canada); Montreal Neurological Institute, Montreal, QC (Canada). McConnell Brain Imaging Centre; Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
University of Gothenburg, Mölndal (Sweden). The Sahlgrenska Academy; Univ. of Pittsburgh, PA (United States)
University of Gothenburg, Mölndal (Sweden). The Sahlgrenska Academy; King's College, London (United Kingdom); National Institute for Health and Care Research (NIHR), London (United KIngdom). Biomedical Research Centre and Maudsley NHS Foundation; Stavanger University Hospital (Norway). Centre for Age-Related Medicine
University of Gothenburg, Mölndal (Sweden). The Sahlgrenska Academy
University of Gothenburg, Mölndal (Sweden). The Sahlgrenska Academy; Univ. College London (United Kingdom). Institute of Neurology and UK Dementia Research Institute; Hong Kong Center for Neurodegenerative Diseases (China); Univ. of Wisconsin, Madison, WI (United States); Sahlgrenska University Hospital, Mölndal (Sweden)
University of Gothenburg, Mölndal (Sweden). The Sahlgrenska Academy; Sahlgrenska University Hospital, Mölndal (Sweden)
Janssen Research & Development, La Jolla, CA (United States). Neuroscience Biomarkers
McGill Univ., Montreal, QC (Canada)

Neuronal dysfunction and cognitive deterioration in Alzheimer's disease (AD) are likely caused by multiple pathophysiological factors. However, mechanistic evidence in humans remains scarce, requiring improved non-invasive techniques and integrative models. We introduce personalized AD computational models built on whole-brain Wilson-Cowan oscillators and incorporating resting-state functional MRI, amyloid-β (Aβ) and tau-PET from 132 individuals in the AD spectrum to evaluate the direct impact of toxic protein deposition on neuronal activity. This subject-specific approach uncovers key patho-mechanistic interactions, including synergistic Aβ and tau effects on cognitive impairment and neuronal excitability increases with disease progression. The data-derived neuronal excitability values strongly predict clinically relevant AD plasma biomarker concentrations (p-tau217, p-tau231, p-tau181, GFAP) and grey matter atrophy obtained through voxel-based morphometry. Furthermore, reconstructed EEG proxy quantities show the hallmark AD electrophysiological alterations (theta band activity enhancement and alpha reductions) which occur with Aβ-positivity and after limbic tau involvement. Microglial activation influences on neuronal activity are less definitive, potentially due to neuroimaging limitations in mapping neuroprotective vs detrimental activation phenotypes. Mechanistic brain activity models can further clarify intricate neurodegenerative processes and accelerate preventive/treatment interventions.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 2396865

Journal Information:: Communications Biology, Journal Name: Communications Biology Journal Issue: 1 Vol. 7; ISSN 2399-3642

Publisher:: Springer NatureCopyright Statement

Country of Publication:: United States

Language:: English

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Integrated transcriptomic and neuroimaging brain model decodes biological mechanisms in aging and Alzheimer’s disease Adewale, Quadri; Khan, Ahmed F.; Carbonell, Felix eLife, Vol. 10 https://doi.org/10.7554/eLife.62589	journal	May 2021
Altered excitatory and inhibitory neuronal subpopulation parameters are distinctly associated with tau and amyloid in Alzheimer’s disease Ranasinghe, Kamalini G.; Verma, Parul; Cai, Chang eLife, Vol. 11 https://doi.org/10.7554/eLife.77850	journal	May 2022