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Predicting longitudinal brain atrophy in Parkinson’s disease using a Susceptible-Infected-Removed agent-based model
Parkinson’s disease is a progressive neurodegenerative disorder characterized by accumulation of abnormal isoforms of alpha-synuclein. Alpha-synuclein is proposed to act as a prion in Parkinson’s disease: In its misfolded pathologic state, it favors the misfolding of normal alpha-synuclein molecules...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MIT Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10473281/ https://www.ncbi.nlm.nih.gov/pubmed/37781140 http://dx.doi.org/10.1162/netn_a_00296 |
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author | Abdelgawad, Alaa Rahayel, Shady Zheng, Ying-Qiu Tremblay, Christina Vo, Andrew Misic, Bratislav Dagher, Alain |
author_facet | Abdelgawad, Alaa Rahayel, Shady Zheng, Ying-Qiu Tremblay, Christina Vo, Andrew Misic, Bratislav Dagher, Alain |
author_sort | Abdelgawad, Alaa |
collection | PubMed |
description | Parkinson’s disease is a progressive neurodegenerative disorder characterized by accumulation of abnormal isoforms of alpha-synuclein. Alpha-synuclein is proposed to act as a prion in Parkinson’s disease: In its misfolded pathologic state, it favors the misfolding of normal alpha-synuclein molecules, spreads trans-neuronally, and causes neuronal 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. In this study, we test this model with longitudinal MRI collected over 4 years from the Parkinson’s Progression Markers Initiative (1,068 T1 MRI scans, 790 Parkinson’s disease scans, and 278 matched control scans). We find that brain deformation progresses in subcortical and cortical regions. The SIR model recapitulates the spatiotemporal distribution of brain atrophy observed in Parkinson’s disease. 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 Parkinson’s disease is consistent with the prion-like hypothesis and that the SIR model is a promising tool to investigate multifactorial neurodegenerative diseases over time. |
format | Online Article Text |
id | pubmed-10473281 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MIT Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-104732812023-10-01 Predicting longitudinal brain atrophy in Parkinson’s disease using a Susceptible-Infected-Removed agent-based model Abdelgawad, Alaa Rahayel, Shady Zheng, Ying-Qiu Tremblay, Christina Vo, Andrew Misic, Bratislav Dagher, Alain Netw Neurosci Research Article Parkinson’s disease is a progressive neurodegenerative disorder characterized by accumulation of abnormal isoforms of alpha-synuclein. Alpha-synuclein is proposed to act as a prion in Parkinson’s disease: In its misfolded pathologic state, it favors the misfolding of normal alpha-synuclein molecules, spreads trans-neuronally, and causes neuronal 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. In this study, we test this model with longitudinal MRI collected over 4 years from the Parkinson’s Progression Markers Initiative (1,068 T1 MRI scans, 790 Parkinson’s disease scans, and 278 matched control scans). We find that brain deformation progresses in subcortical and cortical regions. The SIR model recapitulates the spatiotemporal distribution of brain atrophy observed in Parkinson’s disease. 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 Parkinson’s disease is consistent with the prion-like hypothesis and that the SIR model is a promising tool to investigate multifactorial neurodegenerative diseases over time. MIT Press 2023-10-01 /pmc/articles/PMC10473281/ /pubmed/37781140 http://dx.doi.org/10.1162/netn_a_00296 Text en © 2023 Massachusetts Institute of Technology https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. For a full description of the license, please visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Article Abdelgawad, Alaa Rahayel, Shady Zheng, Ying-Qiu Tremblay, Christina Vo, Andrew Misic, Bratislav Dagher, Alain Predicting longitudinal brain atrophy in Parkinson’s disease using a Susceptible-Infected-Removed agent-based model |
title | Predicting longitudinal brain atrophy in Parkinson’s disease using a Susceptible-Infected-Removed agent-based model |
title_full | Predicting longitudinal brain atrophy in Parkinson’s disease using a Susceptible-Infected-Removed agent-based model |
title_fullStr | Predicting longitudinal brain atrophy in Parkinson’s disease using a Susceptible-Infected-Removed agent-based model |
title_full_unstemmed | Predicting longitudinal brain atrophy in Parkinson’s disease using a Susceptible-Infected-Removed agent-based model |
title_short | Predicting longitudinal brain atrophy in Parkinson’s disease using a Susceptible-Infected-Removed agent-based model |
title_sort | predicting longitudinal brain atrophy in parkinson’s disease using a susceptible-infected-removed agent-based model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10473281/ https://www.ncbi.nlm.nih.gov/pubmed/37781140 http://dx.doi.org/10.1162/netn_a_00296 |
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