A dynamical systems approach for multiscale synthesis of Alzheimer's pathogenesis

Elsevier, Neuron, Volume 111, 19 July 2023
Rollo J., Crawford J., Hardy J.

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.