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Genetic risk factors of Alzheimer’s Disease disrupt resting-state functional connectivity in cognitively intact young individuals
BACKGROUND: Past evidence shows that changes in functional brain connectivity in multiple resting-state networks occur in cognitively healthy individuals who have non-modifiable risk factors for Alzheimer’s Disease. Here, we aimed to investigate how those changes differ in early adulthood and how th...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511575/ https://www.ncbi.nlm.nih.gov/pubmed/37358635 http://dx.doi.org/10.1007/s00415-023-11809-9 |
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author | Kucikova, Ludmila Zeng, Jianmin Muñoz-Neira, Carlos Muniz-Terrera, Graciela Huang, Weijie Gregory, Sarah Ritchie, Craig O’Brien, John Su, Li |
author_facet | Kucikova, Ludmila Zeng, Jianmin Muñoz-Neira, Carlos Muniz-Terrera, Graciela Huang, Weijie Gregory, Sarah Ritchie, Craig O’Brien, John Su, Li |
author_sort | Kucikova, Ludmila |
collection | PubMed |
description | BACKGROUND: Past evidence shows that changes in functional brain connectivity in multiple resting-state networks occur in cognitively healthy individuals who have non-modifiable risk factors for Alzheimer’s Disease. Here, we aimed to investigate how those changes differ in early adulthood and how they might relate to cognition. METHODS: We investigated the effects of genetic risk factors of AD, namely APOEe4 and MAPTA alleles, on resting-state functional connectivity in a cohort of 129 cognitively intact young adults (aged 17–22 years). We used Independent Component Analysis to identify networks of interest, and Gaussian Random Field Theory to compare connectivity between groups. Seed-based analysis was used to quantify inter-regional connectivity strength from the clusters that exhibited significant between-group differences. To investigate the relationship with cognition, we correlated the connectivity and the performance on the Stroop task. RESULTS: The analysis revealed a decrease in functional connectivity in the Default Mode Network (DMN) in both APOEe4 carriers and MAPTA carriers in comparison with non-carriers. APOEe4 carriers showed decreased connectivity in the right angular gyrus (size = 246, p-FDR = 0.0079), which was correlated with poorer performance on the Stroop task. MAPTA carriers showed decreased connectivity in the left middle temporal gyrus (size = 546, p-FDR = 0.0001). In addition, we found that only MAPTA carriers had a decreased connectivity between the DMN and multiple other brain regions. CONCLUSIONS: Our findings indicate that APOEe4 and MAPTA alleles modulate brain functional connectivity in the brain regions within the DMN in cognitively intact young adults. APOEe4 carriers also showed a link between connectivity and cognition. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-023-11809-9. |
format | Online Article Text |
id | pubmed-10511575 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-105115752023-09-22 Genetic risk factors of Alzheimer’s Disease disrupt resting-state functional connectivity in cognitively intact young individuals Kucikova, Ludmila Zeng, Jianmin Muñoz-Neira, Carlos Muniz-Terrera, Graciela Huang, Weijie Gregory, Sarah Ritchie, Craig O’Brien, John Su, Li J Neurol Original Communication BACKGROUND: Past evidence shows that changes in functional brain connectivity in multiple resting-state networks occur in cognitively healthy individuals who have non-modifiable risk factors for Alzheimer’s Disease. Here, we aimed to investigate how those changes differ in early adulthood and how they might relate to cognition. METHODS: We investigated the effects of genetic risk factors of AD, namely APOEe4 and MAPTA alleles, on resting-state functional connectivity in a cohort of 129 cognitively intact young adults (aged 17–22 years). We used Independent Component Analysis to identify networks of interest, and Gaussian Random Field Theory to compare connectivity between groups. Seed-based analysis was used to quantify inter-regional connectivity strength from the clusters that exhibited significant between-group differences. To investigate the relationship with cognition, we correlated the connectivity and the performance on the Stroop task. RESULTS: The analysis revealed a decrease in functional connectivity in the Default Mode Network (DMN) in both APOEe4 carriers and MAPTA carriers in comparison with non-carriers. APOEe4 carriers showed decreased connectivity in the right angular gyrus (size = 246, p-FDR = 0.0079), which was correlated with poorer performance on the Stroop task. MAPTA carriers showed decreased connectivity in the left middle temporal gyrus (size = 546, p-FDR = 0.0001). In addition, we found that only MAPTA carriers had a decreased connectivity between the DMN and multiple other brain regions. CONCLUSIONS: Our findings indicate that APOEe4 and MAPTA alleles modulate brain functional connectivity in the brain regions within the DMN in cognitively intact young adults. APOEe4 carriers also showed a link between connectivity and cognition. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-023-11809-9. Springer Berlin Heidelberg 2023-06-26 2023 /pmc/articles/PMC10511575/ /pubmed/37358635 http://dx.doi.org/10.1007/s00415-023-11809-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Communication Kucikova, Ludmila Zeng, Jianmin Muñoz-Neira, Carlos Muniz-Terrera, Graciela Huang, Weijie Gregory, Sarah Ritchie, Craig O’Brien, John Su, Li Genetic risk factors of Alzheimer’s Disease disrupt resting-state functional connectivity in cognitively intact young individuals |
title | Genetic risk factors of Alzheimer’s Disease disrupt resting-state functional connectivity in cognitively intact young individuals |
title_full | Genetic risk factors of Alzheimer’s Disease disrupt resting-state functional connectivity in cognitively intact young individuals |
title_fullStr | Genetic risk factors of Alzheimer’s Disease disrupt resting-state functional connectivity in cognitively intact young individuals |
title_full_unstemmed | Genetic risk factors of Alzheimer’s Disease disrupt resting-state functional connectivity in cognitively intact young individuals |
title_short | Genetic risk factors of Alzheimer’s Disease disrupt resting-state functional connectivity in cognitively intact young individuals |
title_sort | genetic risk factors of alzheimer’s disease disrupt resting-state functional connectivity in cognitively intact young individuals |
topic | Original Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511575/ https://www.ncbi.nlm.nih.gov/pubmed/37358635 http://dx.doi.org/10.1007/s00415-023-11809-9 |
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