Linking mechanistic multi-scale brain simulation and knowledge technology – towards a holistic understanding of Alzheimer’s Disease

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Recent advantages in storing, organizing, and utilizing scientific knowledge sources open a new field towards a mechanistic understanding of brain diseases. Knowledge bases and ontologies incorporate information about protein-protein interaction, genomic features, and biochemical pathways in health and disease. We explore this topic for Alzheimer’s Disease [1], the most common cause of dementia and one of the leading causes of disability and health-related costs in the world. We show how information from the OMICS scale can be mapped onto the brain [2] and consecutively linked to recent multi-scale brain models of Alzheimer’s Disease that take into account hyperexcitability [3] and its potential usage in the improvement of diagnostic classification [4].


1. Stefanovski, L., et al., Bridging Scales in Alzheimer's Disease: Biological Framework for Brain Simulation With The Virtual Brain. Frontiers in Neuroinformatics, 2021. 15(9).
2. Stefanovski, L., et al., Spatial mapping of subcellular disease pathways and cytoarchitecture to anatomical brain regions for multi‐scale brain simulation with The Virtual Brain. Alzheimer's & Dementia, 2021. 17: p. e052311.
3. Stefanovski, L., et al., Linking Molecular Pathways and Large-Scale Computational Modeling to Assess Candidate Disease Mechanisms and Pharmacodynamics in Alzheimer's Disease. Frontiers in Computational Neuroscience, 2019.
4. Triebkorn, P., et al., Brain simulation augments machine-learning-based classification of dementia. Alzheimers Dement (N Y), 2022. 8(1): p. e12303.