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The impact of genetic risk for Alzheimer’s disease on the structural brain networks of young adults

INTRODUCTION: We investigated the structural brain networks of 562 young adults in relation to polygenic risk for Alzheimer’s disease, using magnetic resonance imaging (MRI) and genotype data from the Avon Longitudinal Study of Parents and Children. METHODS: Diffusion MRI data were used to perform w...

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Autores principales: Mirza-Davies, Anastasia, Foley, Sonya, Caseras, Xavier, Baker, Emily, Holmans, Peter, Escott-Price, Valentina, Jones, Derek K., Harrison, Judith R., Messaritaki, Eirini
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9748570/
https://www.ncbi.nlm.nih.gov/pubmed/36532292
http://dx.doi.org/10.3389/fnins.2022.987677
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author Mirza-Davies, Anastasia
Foley, Sonya
Caseras, Xavier
Baker, Emily
Holmans, Peter
Escott-Price, Valentina
Jones, Derek K.
Harrison, Judith R.
Messaritaki, Eirini
author_facet Mirza-Davies, Anastasia
Foley, Sonya
Caseras, Xavier
Baker, Emily
Holmans, Peter
Escott-Price, Valentina
Jones, Derek K.
Harrison, Judith R.
Messaritaki, Eirini
author_sort Mirza-Davies, Anastasia
collection PubMed
description INTRODUCTION: We investigated the structural brain networks of 562 young adults in relation to polygenic risk for Alzheimer’s disease, using magnetic resonance imaging (MRI) and genotype data from the Avon Longitudinal Study of Parents and Children. METHODS: Diffusion MRI data were used to perform whole-brain tractography and generate structural brain networks for the whole-brain connectome, and for the default mode, limbic and visual subnetworks. The mean clustering coefficient, mean betweenness centrality, characteristic path length, global efficiency and mean nodal strength were calculated for these networks, for each participant. The connectivity of the rich-club, feeder and local connections was also calculated. Polygenic risk scores (PRS), estimating each participant’s genetic risk, were calculated at genome-wide level and for nine specific disease pathways. Correlations were calculated between the PRS and (a) the graph theoretical metrics of the structural networks and (b) the rich-club, feeder and local connectivity of the whole-brain networks. RESULTS: In the visual subnetwork, the mean nodal strength was negatively correlated with the genome-wide PRS (r = –0.19, p = 1.4 × 10(–3)), the mean betweenness centrality was positively correlated with the plasma lipoprotein particle assembly PRS (r = 0.16, p = 5.5 × 10(–3)), and the mean clustering coefficient was negatively correlated with the tau-protein binding PRS (r = –0.16, p = 0.016). In the default mode network, the mean nodal strength was negatively correlated with the genome-wide PRS (r = –0.14, p = 0.044). The rich-club and feeder connectivities were negatively correlated with the genome-wide PRS (r = –0.16, p = 0.035; r = –0.15, p = 0.036). DISCUSSION: We identified small reductions in brain connectivity in young adults at risk of developing Alzheimer’s disease in later life.
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spelling pubmed-97485702022-12-15 The impact of genetic risk for Alzheimer’s disease on the structural brain networks of young adults Mirza-Davies, Anastasia Foley, Sonya Caseras, Xavier Baker, Emily Holmans, Peter Escott-Price, Valentina Jones, Derek K. Harrison, Judith R. Messaritaki, Eirini Front Neurosci Neuroscience INTRODUCTION: We investigated the structural brain networks of 562 young adults in relation to polygenic risk for Alzheimer’s disease, using magnetic resonance imaging (MRI) and genotype data from the Avon Longitudinal Study of Parents and Children. METHODS: Diffusion MRI data were used to perform whole-brain tractography and generate structural brain networks for the whole-brain connectome, and for the default mode, limbic and visual subnetworks. The mean clustering coefficient, mean betweenness centrality, characteristic path length, global efficiency and mean nodal strength were calculated for these networks, for each participant. The connectivity of the rich-club, feeder and local connections was also calculated. Polygenic risk scores (PRS), estimating each participant’s genetic risk, were calculated at genome-wide level and for nine specific disease pathways. Correlations were calculated between the PRS and (a) the graph theoretical metrics of the structural networks and (b) the rich-club, feeder and local connectivity of the whole-brain networks. RESULTS: In the visual subnetwork, the mean nodal strength was negatively correlated with the genome-wide PRS (r = –0.19, p = 1.4 × 10(–3)), the mean betweenness centrality was positively correlated with the plasma lipoprotein particle assembly PRS (r = 0.16, p = 5.5 × 10(–3)), and the mean clustering coefficient was negatively correlated with the tau-protein binding PRS (r = –0.16, p = 0.016). In the default mode network, the mean nodal strength was negatively correlated with the genome-wide PRS (r = –0.14, p = 0.044). The rich-club and feeder connectivities were negatively correlated with the genome-wide PRS (r = –0.16, p = 0.035; r = –0.15, p = 0.036). DISCUSSION: We identified small reductions in brain connectivity in young adults at risk of developing Alzheimer’s disease in later life. Frontiers Media S.A. 2022-11-30 /pmc/articles/PMC9748570/ /pubmed/36532292 http://dx.doi.org/10.3389/fnins.2022.987677 Text en Copyright © 2022 Mirza-Davies, Foley, Caseras, Baker, Holmans, Escott-Price, Jones, Harrison and Messaritaki. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Mirza-Davies, Anastasia
Foley, Sonya
Caseras, Xavier
Baker, Emily
Holmans, Peter
Escott-Price, Valentina
Jones, Derek K.
Harrison, Judith R.
Messaritaki, Eirini
The impact of genetic risk for Alzheimer’s disease on the structural brain networks of young adults
title The impact of genetic risk for Alzheimer’s disease on the structural brain networks of young adults
title_full The impact of genetic risk for Alzheimer’s disease on the structural brain networks of young adults
title_fullStr The impact of genetic risk for Alzheimer’s disease on the structural brain networks of young adults
title_full_unstemmed The impact of genetic risk for Alzheimer’s disease on the structural brain networks of young adults
title_short The impact of genetic risk for Alzheimer’s disease on the structural brain networks of young adults
title_sort impact of genetic risk for alzheimer’s disease on the structural brain networks of young adults
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9748570/
https://www.ncbi.nlm.nih.gov/pubmed/36532292
http://dx.doi.org/10.3389/fnins.2022.987677
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