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Revealing the combi...
Revealing the combined roles of Aβ and tau in Alzheimer's disease via a pathophysiological activity decoder.
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Sanchez-Rodriguez, Lazaro M (author)
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Bezgin, Gleb (author)
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Carbonell, Felix (author)
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Therriault, Joseph (author)
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Fernandez-Arias, Jaime (author)
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Servaes, Stijn (author)
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Rahmouni, Nesrine (author)
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Tissot, Cecile (author)
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Stevenson, Jenna (author)
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- Karikari, Thomas (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Ashton, Nicholas J. (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Lessa Benedet, Andréa (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Blennow, Kaj, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Triana-Baltzer, Gallen (author)
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Kolb, Hartmuth C (author)
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Rosa-Neto, Pedro (author)
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Iturria-Medina, Yasser (author)
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(creator_code:org_t)
- Cold Spring Harbor Laboratory, 2023
- 2023
- English.
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In: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
- Related links:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Neuronal dysfunction and cognitive deterioration in Alzheimer's disease (AD) are likely caused by multiple pathophysiological factors. However, evidence in humans remains scarce, necessitating improved non-invasive techniques and integrative mechanistic models. Here, we introduce personalized brain activity models incorporating functional MRI, amyloid-β (Aβ) and tau-PET from AD-related participants (N=132). Within the model assumptions, electrophysiological activity is mediated by toxic protein deposition. Our integrative 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). Furthermore, our results reproduce 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 phenotypes. Mechanistic brain activity models can further clarify intricate neurodegenerative processes and accelerate preventive/treatment interventions.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Publication and Content Type
- vet (subject category)
- art (subject category)
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- By the author/editor
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Sanchez-Rodrigue ...
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Bezgin, Gleb
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Carbonell, Felix
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Therriault, Jose ...
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Fernandez-Arias, ...
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Servaes, Stijn
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show more...
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Rahmouni, Nesrin ...
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Tissot, Cecile
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Stevenson, Jenna
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Karikari, Thomas
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Ashton, Nicholas ...
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Lessa Benedet, A ...
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Zetterberg, Henr ...
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Blennow, Kaj, 19 ...
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Triana-Baltzer, ...
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Kolb, Hartmuth C
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Rosa-Neto, Pedro
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Iturria-Medina, ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
- bioRxiv : the pr ...
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University of Gothenburg