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Multiple genetic imaging study of the association between cholesterol metabolism and brain functional alterations in individuals with risk factors for Alzheimer's disease
Alzheimer's disease (AD) is a clinically and genetically heterogeneous neurodegenerative disease. Genes involved in cholesterol metabolism may play a role in the pathological changes of AD. However, the imaging genetics-based endophenotypes derived from polymorphisms in multiple functionally re...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941243/ https://www.ncbi.nlm.nih.gov/pubmed/26985771 http://dx.doi.org/10.18632/oncotarget.8100 |
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author | Bai, Feng Yuan, Yonggui Shi, Yongmei Zhang, Zhijun |
author_facet | Bai, Feng Yuan, Yonggui Shi, Yongmei Zhang, Zhijun |
author_sort | Bai, Feng |
collection | PubMed |
description | Alzheimer's disease (AD) is a clinically and genetically heterogeneous neurodegenerative disease. Genes involved in cholesterol metabolism may play a role in the pathological changes of AD. However, the imaging genetics-based endophenotypes derived from polymorphisms in multiple functionally related genes are unclear in individuals with risk factors for AD. Forty-three amnestic mild cognitive impairment (aMCI) subjects and 30 healthy controls underwent resting-state functional magnetic resonance imaging (fMRI) measurements of brain topological organization. Thirty-three previously suggested tagging single nucleotide polymorphisms (SNPs) from 12 candidate genes in the cholesterol metabolism pathway were further investigated. A cholesterol metabolism pathway gene-based imaging genetics approach was then utilized to investigate disease-related differences between the groups based on genotype-by-aMCI interactions. The cholesterol metabolism pathway genes exerted widespread effects on the cortico-subcortical-cerebellar spontaneous brain activity. Meanwhile, left lateralization of global brain connectivity was associated with cholesterol metabolism pathway genes. The APOE rs429358 variation significantly influenced the brain network characteristics, affecting the activation of nodes as well as the connectivity of edges in aMCI subjects. The cholesterol metabolism pathway gene-based imaging genetics approach may provide new opportunities to understand the mechanisms underlying AD and suggested that APOE rs429358 is a core genetic variation that is associated with disease-related differences in brain function. |
format | Online Article Text |
id | pubmed-4941243 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-49412432016-07-19 Multiple genetic imaging study of the association between cholesterol metabolism and brain functional alterations in individuals with risk factors for Alzheimer's disease Bai, Feng Yuan, Yonggui Shi, Yongmei Zhang, Zhijun Oncotarget Research Paper: Gerotarget (Focus on Aging) Alzheimer's disease (AD) is a clinically and genetically heterogeneous neurodegenerative disease. Genes involved in cholesterol metabolism may play a role in the pathological changes of AD. However, the imaging genetics-based endophenotypes derived from polymorphisms in multiple functionally related genes are unclear in individuals with risk factors for AD. Forty-three amnestic mild cognitive impairment (aMCI) subjects and 30 healthy controls underwent resting-state functional magnetic resonance imaging (fMRI) measurements of brain topological organization. Thirty-three previously suggested tagging single nucleotide polymorphisms (SNPs) from 12 candidate genes in the cholesterol metabolism pathway were further investigated. A cholesterol metabolism pathway gene-based imaging genetics approach was then utilized to investigate disease-related differences between the groups based on genotype-by-aMCI interactions. The cholesterol metabolism pathway genes exerted widespread effects on the cortico-subcortical-cerebellar spontaneous brain activity. Meanwhile, left lateralization of global brain connectivity was associated with cholesterol metabolism pathway genes. The APOE rs429358 variation significantly influenced the brain network characteristics, affecting the activation of nodes as well as the connectivity of edges in aMCI subjects. The cholesterol metabolism pathway gene-based imaging genetics approach may provide new opportunities to understand the mechanisms underlying AD and suggested that APOE rs429358 is a core genetic variation that is associated with disease-related differences in brain function. Impact Journals LLC 2016-03-15 /pmc/articles/PMC4941243/ /pubmed/26985771 http://dx.doi.org/10.18632/oncotarget.8100 Text en Copyright: © 2016 Bai et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper: Gerotarget (Focus on Aging) Bai, Feng Yuan, Yonggui Shi, Yongmei Zhang, Zhijun Multiple genetic imaging study of the association between cholesterol metabolism and brain functional alterations in individuals with risk factors for Alzheimer's disease |
title | Multiple genetic imaging study of the association between cholesterol metabolism and brain functional alterations in individuals with risk factors for Alzheimer's disease |
title_full | Multiple genetic imaging study of the association between cholesterol metabolism and brain functional alterations in individuals with risk factors for Alzheimer's disease |
title_fullStr | Multiple genetic imaging study of the association between cholesterol metabolism and brain functional alterations in individuals with risk factors for Alzheimer's disease |
title_full_unstemmed | Multiple genetic imaging study of the association between cholesterol metabolism and brain functional alterations in individuals with risk factors for Alzheimer's disease |
title_short | Multiple genetic imaging study of the association between cholesterol metabolism and brain functional alterations in individuals with risk factors for Alzheimer's disease |
title_sort | multiple genetic imaging study of the association between cholesterol metabolism and brain functional alterations in individuals with risk factors for alzheimer's disease |
topic | Research Paper: Gerotarget (Focus on Aging) |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941243/ https://www.ncbi.nlm.nih.gov/pubmed/26985771 http://dx.doi.org/10.18632/oncotarget.8100 |
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