Rollo, J;
Crawford, J;
Hardy, J;
(2023)
A dynamical systems approach for multiscale synthesis of Alzheimer's pathogenesis.
Neuron
, 111
(14)
pp. 2126-2139.
10.1016/j.neuron.2023.04.018.
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Abstract
Alzheimer's disease (AD) is a spatially dynamic pathology that implicates a growing volume of multiscale data spanning genetic, cellular, tissue, and organ levels of the organization. These data and bioinformatics analyses provide clear evidence for the interactions within and between these levels. The resulting heterarchy precludes a linear neuron-centric approach and necessitates that the numerous interactions are measured in a way that predicts their impact on the emergent dynamics of the disease. This level of complexity confounds intuition, and we propose a new methodology that uses non-linear dynamical systems modeling to augment intuition and that links with a community-wide participatory platform to co-create and test system-level hypotheses and interventions. In addition to enabling the integration of multiscale knowledge, key benefits include a more rapid innovation cycle and a rational process for prioritization of data campaigns. We argue that such an approach is essential to support the discovery of multilevel-coordinated polypharmaceutical interventions.
| Type: | Article |
|---|---|
| Title: | A dynamical systems approach for multiscale synthesis of Alzheimer's pathogenesis |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.neuron.2023.04.018 |
| Publisher version: | https://doi.org/10.1016/j.neuron.2023.04.018 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Alzheimer’s disease, data prioritization, dementia, dynamical systems modeling, mathematical modeling, multiscale data, open innovation ecosystem, participatory methodology, systems biology, systems pathology |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10180043 |
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