Computational modelling of pathogenic protein behaviour-governing mechanisms in the brain

Konstantinos Georgiadis, Alexandra L. Young, Michael Hütel, Adeel Razi, Carla Semedo, Jonathan Schott, Sébastien Ourselin, Jason D. Warren, Marc Modat

Research output: Chapter in Book/Report/Conference proceedingConference PaperResearchpeer-review

Abstract

Most neurodegenerative diseases are caused by pathogenic proteins. Pathogenic protein behaviour is governed by neurobiological mechanisms which cause them to spread and accumulate in the brain, leading to cellular death and eventually atrophy. Patient data suggests atrophy loosely follows a number of spatiotemporal patterns, with different patterns associated with each neurodegenerative disease variant. It is hypothesised that the behaviour of different pathogenic protein variants is governed by different mechanisms, which could explain the pattern variety. Machine learning approaches take advantage of the pattern predictability for differential diagnosis and prognosis, but are unable to reveal new information on the underlying mechanisms, which are still poorly understood. We propose a framework where computational models of these mechanisms were created based on neurobiological literature. Competing hypotheses regarding the mechanisms were modelled and the outcomes evaluated against empirical data of Alzheimer’s disease. With this approach, we are able to characterise the impact of each mechanism on the neurodegenerative process. We also demonstrate how our framework could evaluate candidate therapies.

Original languageEnglish
Title of host publicationProceedings of Medical Image Computing and Computer Assisted Intervention - MICCAI 2018
EditorsAlejandro F. Frangi, Julia A. Schnabel, Christos Davatzikos, Carlos Alberola-Lopez, Gabor Fichtinger
Place of PublicationSwitzerland
PublisherSpringer
Pages532-539
Number of pages8
ISBN (Electronic)9783030009311
ISBN (Print)9783030009304
DOIs
Publication statusPublished - 2018
Externally publishedYes
EventMedical Image Computing and Computer-Assisted Intervention 2018 - Granada, Spain
Duration: 16 Sep 201820 Sep 2018
Conference number: 21st
https://www.miccai2018.org/en/

Publication series

NameLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Volume11072 LNCS
ISSN (Print)0302-9743
ISSN (Electronic)1611-3349

Conference

ConferenceMedical Image Computing and Computer-Assisted Intervention 2018
Abbreviated titleMICCAI 2018
CountrySpain
CityGranada
Period16/09/1820/09/18
Internet address

Keywords

  • Computational modelling
  • Neurodegenerative disease

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