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Polygenic Hazard Score Associated Multimodal Brain Networks Along the Alzheimer’s Disease Continuum
BACKGROUND: Late-onset Alzheimer’s disease (AD) is a polygenic neurodegenerative disease. Identifying the neuroimaging phenotypes behind the genetic predisposition of AD is critical to the understanding of AD pathogenesis. Two major questions which previous studies have led to are: (1) should the ge...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446666/ https://www.ncbi.nlm.nih.gov/pubmed/34539385 http://dx.doi.org/10.3389/fnagi.2021.725246 |
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author | Li, Kaicheng Fu, Zening Qi, Shile Luo, Xiao Zeng, Qingze Xu, Xiaopei Huang, Peiyu Zhang, Minming Calhoun, Vince D. |
author_facet | Li, Kaicheng Fu, Zening Qi, Shile Luo, Xiao Zeng, Qingze Xu, Xiaopei Huang, Peiyu Zhang, Minming Calhoun, Vince D. |
author_sort | Li, Kaicheng |
collection | PubMed |
description | BACKGROUND: Late-onset Alzheimer’s disease (AD) is a polygenic neurodegenerative disease. Identifying the neuroimaging phenotypes behind the genetic predisposition of AD is critical to the understanding of AD pathogenesis. Two major questions which previous studies have led to are: (1) should the general “polygenic hazard score” (PHS) be a good choice to identify the individual genetic risk for AD; and (2) should researchers also include inter-modality relationships in the analyses considering these may provide complementary information about the AD etiology. METHODS: We collected 88 healthy controls, 77 patients with mild cognitive impairment (MCI), and 22 AD patients to simulate the AD continuum included from the ADNI database. PHS-guided multimodal fusion was used to investigate the impact of PHS on multimodal brain networks in AD-continuum by maximizing both inter-modality association and reference-modality correlation. Fractional amplitude of low frequency fluctuations, gray matter (GM) volume, and amyloid standard uptake value ratios were included as neuroimaging features. Eventually, the changes in neuroimaging features along AD continuum were investigated, and relationships between cognitive performance and identified PHS associated multimodal components were established. RESULTS: We found that PHS was associated with multimodal brain networks, which showed different functional and structural impairments under increased amyloid deposits. Notably, along with AD progression, functional impairment occurred before GM atrophy, amyloid deposition started from the MCI stage and progressively increased throughout the disease continuum. CONCLUSION: PHS is associated with multi-facets of brain impairments along the AD continuum, including cognitive dysfunction, pathological deposition, which might underpin the AD pathogenesis. |
format | Online Article Text |
id | pubmed-8446666 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84466662021-09-18 Polygenic Hazard Score Associated Multimodal Brain Networks Along the Alzheimer’s Disease Continuum Li, Kaicheng Fu, Zening Qi, Shile Luo, Xiao Zeng, Qingze Xu, Xiaopei Huang, Peiyu Zhang, Minming Calhoun, Vince D. Front Aging Neurosci Neuroscience BACKGROUND: Late-onset Alzheimer’s disease (AD) is a polygenic neurodegenerative disease. Identifying the neuroimaging phenotypes behind the genetic predisposition of AD is critical to the understanding of AD pathogenesis. Two major questions which previous studies have led to are: (1) should the general “polygenic hazard score” (PHS) be a good choice to identify the individual genetic risk for AD; and (2) should researchers also include inter-modality relationships in the analyses considering these may provide complementary information about the AD etiology. METHODS: We collected 88 healthy controls, 77 patients with mild cognitive impairment (MCI), and 22 AD patients to simulate the AD continuum included from the ADNI database. PHS-guided multimodal fusion was used to investigate the impact of PHS on multimodal brain networks in AD-continuum by maximizing both inter-modality association and reference-modality correlation. Fractional amplitude of low frequency fluctuations, gray matter (GM) volume, and amyloid standard uptake value ratios were included as neuroimaging features. Eventually, the changes in neuroimaging features along AD continuum were investigated, and relationships between cognitive performance and identified PHS associated multimodal components were established. RESULTS: We found that PHS was associated with multimodal brain networks, which showed different functional and structural impairments under increased amyloid deposits. Notably, along with AD progression, functional impairment occurred before GM atrophy, amyloid deposition started from the MCI stage and progressively increased throughout the disease continuum. CONCLUSION: PHS is associated with multi-facets of brain impairments along the AD continuum, including cognitive dysfunction, pathological deposition, which might underpin the AD pathogenesis. Frontiers Media S.A. 2021-09-03 /pmc/articles/PMC8446666/ /pubmed/34539385 http://dx.doi.org/10.3389/fnagi.2021.725246 Text en Copyright © 2021 Li, Fu, Qi, Luo, Zeng, Xu, Huang, Zhang and Calhoun. 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 Li, Kaicheng Fu, Zening Qi, Shile Luo, Xiao Zeng, Qingze Xu, Xiaopei Huang, Peiyu Zhang, Minming Calhoun, Vince D. Polygenic Hazard Score Associated Multimodal Brain Networks Along the Alzheimer’s Disease Continuum |
title | Polygenic Hazard Score Associated Multimodal Brain Networks Along the Alzheimer’s Disease Continuum |
title_full | Polygenic Hazard Score Associated Multimodal Brain Networks Along the Alzheimer’s Disease Continuum |
title_fullStr | Polygenic Hazard Score Associated Multimodal Brain Networks Along the Alzheimer’s Disease Continuum |
title_full_unstemmed | Polygenic Hazard Score Associated Multimodal Brain Networks Along the Alzheimer’s Disease Continuum |
title_short | Polygenic Hazard Score Associated Multimodal Brain Networks Along the Alzheimer’s Disease Continuum |
title_sort | polygenic hazard score associated multimodal brain networks along the alzheimer’s disease continuum |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446666/ https://www.ncbi.nlm.nih.gov/pubmed/34539385 http://dx.doi.org/10.3389/fnagi.2021.725246 |
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