Instruct: Identify the main category of Medrxiv papers based on the titles and abstracts
Query: Predicting longitudinal brain atrophy in Parkinson's disease using a Susceptible-Infected-Removed agent-based model Parkinsons disease (PD) is a progressive neurodegenerative disorder characterized by accumulation of abnormal isoforms of alpha-synuclein. Alpha-synuclein is proposed to act as a prion in PD: in its misfolded pathologic state it favours the misfolding of normal alpha-synuclein molecules, spreads trans-neuronally, and causes neuronal or synaptic damage as it accumulates. This theory remains controversial. We have previously developed a Susceptible-Infected-Removed (SIR) computational model that simulates the templating, propagation and toxicity of alpha-synuclein molecules in the brain. Here we test this model with longitudinal MRI collected over four years from the Parkinson Progression Markers Initiative (1068 T1 MRI scans, 790 PD, 278 matched controls). We find that brain deformation progresses in subcortical and cortical regions. The SIR model, using structural connectivity from diffusion MRI, recapitulates the spatiotemporal distribution of brain atrophy observed in PD. We show that connectome topology and geometry significantly contribute to model fit. We also show that the spatial expression of two genes implicated in alpha-synuclein synthesis and clearance, SNCA and GBA, also influences the atrophy pattern. We conclude that the progression of atrophy in PD is consistent with the prion-like hypothesis and that the SIR model is a promising tool to investigate multifactorial neurodegenerative diseases over time.
41
The categories of this paper are: nephrology
45
The categories of this paper are: pharmacology
5
The categories of this paper are: health
67
The categories of this paper are: transplantation
2
The categories of this paper are: medicine
53
The categories of this paper are: pathology
71
The categories of this paper are: ethics
62
The categories of this paper are: orthopedics
6
The categories of this paper are: and
51
The categories of this paper are: education
25
The categories of this paper are: improvement
44
The categories of this paper are: endocrinology
46
The categories of this paper are: therapeutics
34
The categories of this paper are: therapy
16
The categories of this paper are: immunology
27
The categories of this paper are: quality