  Models of misfolded proteins (MP) aim at discovering the bio-mechanical
propagation properties of neurological diseases (ND) by identifying plausible
associated dynamical systems. Solving these systems along the full disease
trajectory is usually challenging, due to the lack of a well defined time axis
for the pathology. This issue is addressed by disease progression models (DPM)
where long-term progression trajectories are estimated via time
reparametrization of individual observations. However, due to their loose
assumptions on the dynamics, DPM do not provide insights on the bio-mechanical
properties of MP propagation. Here we propose a unified model of
spatio-temporal protein dynamics based on the joint estimation of long-term MP
dynamics and time reparameterization of individuals observations. The model is
expressed within a Gaussian Process (GP) regression setting, where constraints
on the MP dynamics are imposed through non--linear dynamical systems. We use
stochastic variational inference on both GP and dynamical system parameters for
scalable inference and uncertainty quantification of the trajectories.
Experiments on simulated data show that our model accurately recovers
prescribed rates along graph dynamics and precisely reconstructs the underlying
progression. When applied to brain imaging data our model allows the
bio-mechanical interpretation of amyloid deposition in Alzheimer's disease,
leading to plausible simulations of MP propagation, and achieving accurate
predictions of individual MP deposition in unseen data.
