Misfolded Protein spreading through connectome

[alecrimi]

Misfolded protein spreading through brain connectome

Project Description

Connectomics have been used so far to look for quantifying global and local differences in the functional or structural brain networks, or alternatively, to simulate/study brain hemodynamics. Very few studies have used connectomes to investigate the spreading of misfolded proteins which is at the basis of Parkinson’s (PD) and Alzheimer’s disease (AD). It is believed that diseases as AD and PD are spread by misfolded proteins or agents which moves along brain connections (axons and dendrides of the neurons) starting from specific regions to others. For instance, AD has a progression of tau pathology consistently beginning in the entorhinal cortex, the locus coeruleus, and other nearby noradrenergic brainstem nuclei, before spreading to the rest of the limbic system as well as the cacingulate and retrosplenial cortices. While Parkinsons starts from the brainstem and spread to the neocortex. A previous study investigated this mechanism on connectome comparing simulated tau deposits on connectome to those detected by PET scans specific for Alzheimer’s. In this project, we aim at carrying out a similar study but for PD relating to brain atrophy. In particular, we want to simulate deposits/spreading of alpha-syn proceeding via the brain’s anatomic connectivity network. We will use human and mice data provided by the supervisors. The main challenge of the project is defining a proper model of spreading along the connectome. Data from the ADNI and PPMI dataset and given by the project supervisors will be given. Those include case (PD and AD patients) and control subjects along with clinical data and genetics (see below).
Current challenges also include proper brain extraction (E.g. FSL BET) of PET data.

Skills required to participate

Python : coders
Genetic data: people who can handle SNP dataset
Mathematics: people who can manage dynamical models, heat equation and so on

Integration

How would your project integrate a neuroimager/clinician/psychologist/computational scientist/maker/artist as collaborator?
We want to simulate pathological brian disease comparing simulation of pathogen agents on structual connectomes to known neuroimaging markers as brain-atrophy and deposits from PET data.

Try to define intermediate goals (milestones).

1. Compare simulations on Parkinson data to brain atrophy (after checking that the atrophy has been obtained properly)
2. Compare simulations on Alzheimer data to BetaAmyloid PET deposits (after checking that the deposits has been obtained properly)
3. Develop or improve existing spreading models.

Preparation material

1. Crimi and Kara "SPREADING MODEL FOR PATIENTS WITH PARKINSON'S DISEASE BASED ON CONNECTIVITY DIFFERENCES" IEEE ISBI 2019,
   https://www.researchgate.net/publication/333583009_SPREADING_MODEL_FOR_PATIENTS_WITH_PARKINSON%27S_DISEASE_BASED_ON_CONNECTIVITY_DIFFERENCES

2. Iturria-Medina, Yasser, et al. “Epidemic spreading model to characterize misfolded proteins propagation in aging and associated neurodegenerative disorders.” PLoS computational biology 10.11 (2014): e1003956. https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003956

3. Raj, Ashish, Amy Kuceyeski, and Michael Weiner. “A network diffusion model of disease progression in dementia.” Neuron73.6 (2012): 1204-1215. https://www.sciencedirect.com/science/article/pii/S0896627312001353

4. H. Braak et al., “Staging of brain pathology related to sporadic Parkinsons disease,” Neurobiology of aging, vol. 24, no. 2, pp. 197–211, 2003. https://www.sciencedirect.com/science/article/pii/S0197458002000659

Link to your GitHub repo

Starting stuff to use:
https://github.com/alecrimi/misfoldedproiteins_connectome

Communication

Slack channel: https://mattermost.brainhack.org/brainhack/channels/misfoldedproteins

[rmarkello]

Hi @alecrimi ! This looks really cool. I though that you might want to check out a related project and preprint by the inimitable @yingqiuz. I don't think she's at the OHBM hackathon, but she's usually pretty responsive on GitHub 😄 I'd also be happy to chat about her work since I'm somewhat familiar with it.