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Genetic basis of anatomical asymmetry and aberrant dynamic functional networks in Alzheimer’s disease

Nicolás Rubido Orcid Logo, Gernot Riedel Orcid Logo, Vesna Vuksanovic Orcid Logo

Brain Communications, Volume: 6, Issue: 1

Swansea University Author: Vesna Vuksanovic Orcid Logo

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DOI (Published version): 10.1093/braincomms/fcad320

Abstract

Genetic associations with macroscopic brain networks can provide insights into healthy and aberrant cortical connectivity in disease. However, associations specific to dynamic functional connectivity in Alzheimer’s disease are still largely unexplored. Understanding the association between gene expr...

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Published in: Brain Communications
ISSN: 2632-1297
Published: Oxford University Press (OUP) 2023
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URI: https://cronfa.swan.ac.uk/Record/cronfa65252
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Our analyses include genetic variations associated with Alzheimer’s disease and also genetic variants expressed within the cholinergic brain pathways. Our findings show that contrasts in metastability of functional networks between Alzheimer’s and healthy individuals can in part be explained by the two combinations of genetic co-variations in the brain with the confidence interval between 72% and 92%. The highly central nodes, driving the brain aberrant metastable dynamics in Alzheimer’s disease, highly correlate with the magnitude of variations from two combinations of genes expressed in the brain. These nodes include mainly the white matter, parietal and occipital brain regions, each of which (or their combinations) are involved in impaired cognitive function in Alzheimer’s disease. In addition, our results provide evidence of the role of genetic associations across brain regions in asymmetric changes in ageing. 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spelling v2 65252 2023-12-08 Genetic basis of anatomical asymmetry and aberrant dynamic functional networks in Alzheimer’s disease a1a6e2bd0b6ee99f648abb6201dea474 0000-0003-4655-698X Vesna Vuksanovic Vesna Vuksanovic true false 2023-12-08 HDAT Genetic associations with macroscopic brain networks can provide insights into healthy and aberrant cortical connectivity in disease. However, associations specific to dynamic functional connectivity in Alzheimer’s disease are still largely unexplored. Understanding the association between gene expression in the brain and functional networks may provide useful information about the molecular processes underlying variations in impaired brain function. Given the potential of dynamic functional connectivity to uncover brain states associated with Alzheimer’s disease, it is interesting to ask: How does gene expression associated with Alzheimer’s disease map onto the dynamic functional brain connectivity? If genetic variants associated with neurodegenerative processes involved in Alzheimer’s disease are to be correlated with brain function, it is essential to generate such a map. Here, we investigate how the relation between gene expression in the brain and dynamic functional connectivity arises from nodal interactions, quantified by their role in network centrality (i.e. the drivers of the metastability), and the principal component of genetic co-expression across the brain. Our analyses include genetic variations associated with Alzheimer’s disease and also genetic variants expressed within the cholinergic brain pathways. Our findings show that contrasts in metastability of functional networks between Alzheimer’s and healthy individuals can in part be explained by the two combinations of genetic co-variations in the brain with the confidence interval between 72% and 92%. The highly central nodes, driving the brain aberrant metastable dynamics in Alzheimer’s disease, highly correlate with the magnitude of variations from two combinations of genes expressed in the brain. These nodes include mainly the white matter, parietal and occipital brain regions, each of which (or their combinations) are involved in impaired cognitive function in Alzheimer’s disease. In addition, our results provide evidence of the role of genetic associations across brain regions in asymmetric changes in ageing. We validated our findings on the same cohort using alternative brain parcellation methods. This work demonstrates how genetic variations underpin aberrant dynamic functional connectivity in Alzheimer’s disease. Journal Article Brain Communications 6 1 Oxford University Press (OUP) 2632-1297 dynamic functional connectivity, genetic risk, cholinergic pathway, Alzheimer’s disease 3 12 2023 2023-12-03 10.1093/braincomms/fcad320 COLLEGE NANME Health Data Science COLLEGE CODE HDAT Swansea University This work is supported by funds from Roland Sutton Academic Trust (RG:#RG13688 and #DSR1058-100). 2024-04-10T11:49:46.2813098 2023-12-08T12:01:40.4693858 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Health Data Science Nicolás Rubido 0000-0002-0616-2479 1 Gernot Riedel 0000-0002-2374-6281 2 Vesna Vuksanovic 0000-0003-4655-698X 3 65252__29380__3608161957ec434c9ffdc80e9377719f.pdf 65252.pdf 2024-01-04T15:33:08.3657503 Output 1723521 application/pdf Version of Record true This is an Open Access article distributed under the terms of the Creative Commons Attribution License. true eng https://creativecommons.org/licenses/by/4.0/ 223
title Genetic basis of anatomical asymmetry and aberrant dynamic functional networks in Alzheimer’s disease
spellingShingle Genetic basis of anatomical asymmetry and aberrant dynamic functional networks in Alzheimer’s disease
Vesna Vuksanovic
title_short Genetic basis of anatomical asymmetry and aberrant dynamic functional networks in Alzheimer’s disease
title_full Genetic basis of anatomical asymmetry and aberrant dynamic functional networks in Alzheimer’s disease
title_fullStr Genetic basis of anatomical asymmetry and aberrant dynamic functional networks in Alzheimer’s disease
title_full_unstemmed Genetic basis of anatomical asymmetry and aberrant dynamic functional networks in Alzheimer’s disease
title_sort Genetic basis of anatomical asymmetry and aberrant dynamic functional networks in Alzheimer’s disease
author_id_str_mv a1a6e2bd0b6ee99f648abb6201dea474
author_id_fullname_str_mv a1a6e2bd0b6ee99f648abb6201dea474_***_Vesna Vuksanovic
author Vesna Vuksanovic
author2 Nicolás Rubido
Gernot Riedel
Vesna Vuksanovic
format Journal article
container_title Brain Communications
container_volume 6
container_issue 1
publishDate 2023
institution Swansea University
issn 2632-1297
doi_str_mv 10.1093/braincomms/fcad320
publisher Oxford University Press (OUP)
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Health Data Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Health Data Science
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description Genetic associations with macroscopic brain networks can provide insights into healthy and aberrant cortical connectivity in disease. However, associations specific to dynamic functional connectivity in Alzheimer’s disease are still largely unexplored. Understanding the association between gene expression in the brain and functional networks may provide useful information about the molecular processes underlying variations in impaired brain function. Given the potential of dynamic functional connectivity to uncover brain states associated with Alzheimer’s disease, it is interesting to ask: How does gene expression associated with Alzheimer’s disease map onto the dynamic functional brain connectivity? If genetic variants associated with neurodegenerative processes involved in Alzheimer’s disease are to be correlated with brain function, it is essential to generate such a map. Here, we investigate how the relation between gene expression in the brain and dynamic functional connectivity arises from nodal interactions, quantified by their role in network centrality (i.e. the drivers of the metastability), and the principal component of genetic co-expression across the brain. Our analyses include genetic variations associated with Alzheimer’s disease and also genetic variants expressed within the cholinergic brain pathways. Our findings show that contrasts in metastability of functional networks between Alzheimer’s and healthy individuals can in part be explained by the two combinations of genetic co-variations in the brain with the confidence interval between 72% and 92%. The highly central nodes, driving the brain aberrant metastable dynamics in Alzheimer’s disease, highly correlate with the magnitude of variations from two combinations of genes expressed in the brain. These nodes include mainly the white matter, parietal and occipital brain regions, each of which (or their combinations) are involved in impaired cognitive function in Alzheimer’s disease. In addition, our results provide evidence of the role of genetic associations across brain regions in asymmetric changes in ageing. We validated our findings on the same cohort using alternative brain parcellation methods. This work demonstrates how genetic variations underpin aberrant dynamic functional connectivity in Alzheimer’s disease.
published_date 2023-12-03T11:49:43Z
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