Neuromorphic deviations associated with transcriptomic expression and specific cell type in Alzheimer’s disease

Abstract Alzheimer’s disease (AD) is known to be associated with cortical anatomical atrophy and neurodegeneration across various brain regions. However, the relationships between brain structural changes in AD and gene expression remain unclear. We perform the morphometric similarity network (MSN)...

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Main Authors: Jinzhong Peng, Qin Tang, Yilu Li, Lin Liu, Bharat Bhusan Biswal, Pan Wang
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-90872-w
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author Jinzhong Peng
Qin Tang
Yilu Li
Lin Liu
Bharat Bhusan Biswal
Pan Wang
author_facet Jinzhong Peng
Qin Tang
Yilu Li
Lin Liu
Bharat Bhusan Biswal
Pan Wang
author_sort Jinzhong Peng
collection DOAJ
description Abstract Alzheimer’s disease (AD) is known to be associated with cortical anatomical atrophy and neurodegeneration across various brain regions. However, the relationships between brain structural changes in AD and gene expression remain unclear. We perform the morphometric similarity network (MSN) analysis to reveal the consistent cortical structural differences in individuals with AD compared to controls, and investigate the associations between brain-wide gene expression and morphometric changes. Furthermore, we identify abnormally MSN-related genes linked to specific cell types as the major contributors to transcriptomic relationships. MSN-related structural changes are located in the lateral ventral prefrontal cortex, temporal pole and medial prefrontal lobe, which are highly associated with the AD’s cognitive decline. Analysis of gene expression shows the spatial correlations between AD-related genes and MSN differences. Examination of cell type-specific signature genes indicates that changes in microglia and neuronal transcriptional profiles largely contribute to AD-specific MSN differences. The study map the disease-specific structural alterations in AD down to the cellular level, offering a novel perspective on the linking surface-level changes to molecular mechanisms.
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spelling doaj-art-9fb2aec58bd04670ad450d2fdd70946a2025-08-20T02:59:20ZengNature PortfolioScientific Reports2045-23222025-03-0115111110.1038/s41598-025-90872-wNeuromorphic deviations associated with transcriptomic expression and specific cell type in Alzheimer’s diseaseJinzhong Peng0Qin Tang1Yilu Li2Lin Liu3Bharat Bhusan Biswal4Pan Wang5The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, Center for Information in Medicine, School of Life Science and Technology, University of Electronic Science and Technology of ChinaThe Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, Center for Information in Medicine, School of Life Science and Technology, University of Electronic Science and Technology of ChinaThe Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, Center for Information in Medicine, School of Life Science and Technology, University of Electronic Science and Technology of ChinaThe Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, Center for Information in Medicine, School of Life Science and Technology, University of Electronic Science and Technology of ChinaThe Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, Center for Information in Medicine, School of Life Science and Technology, University of Electronic Science and Technology of ChinaThe Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, Center for Information in Medicine, School of Life Science and Technology, University of Electronic Science and Technology of ChinaAbstract Alzheimer’s disease (AD) is known to be associated with cortical anatomical atrophy and neurodegeneration across various brain regions. However, the relationships between brain structural changes in AD and gene expression remain unclear. We perform the morphometric similarity network (MSN) analysis to reveal the consistent cortical structural differences in individuals with AD compared to controls, and investigate the associations between brain-wide gene expression and morphometric changes. Furthermore, we identify abnormally MSN-related genes linked to specific cell types as the major contributors to transcriptomic relationships. MSN-related structural changes are located in the lateral ventral prefrontal cortex, temporal pole and medial prefrontal lobe, which are highly associated with the AD’s cognitive decline. Analysis of gene expression shows the spatial correlations between AD-related genes and MSN differences. Examination of cell type-specific signature genes indicates that changes in microglia and neuronal transcriptional profiles largely contribute to AD-specific MSN differences. The study map the disease-specific structural alterations in AD down to the cellular level, offering a novel perspective on the linking surface-level changes to molecular mechanisms.https://doi.org/10.1038/s41598-025-90872-wAlzheimer’s diseaseCognitive declineCell typesMorphometric similarity networkGene expression
spellingShingle Jinzhong Peng
Qin Tang
Yilu Li
Lin Liu
Bharat Bhusan Biswal
Pan Wang
Neuromorphic deviations associated with transcriptomic expression and specific cell type in Alzheimer’s disease
Scientific Reports
Alzheimer’s disease
Cognitive decline
Cell types
Morphometric similarity network
Gene expression
title Neuromorphic deviations associated with transcriptomic expression and specific cell type in Alzheimer’s disease
title_full Neuromorphic deviations associated with transcriptomic expression and specific cell type in Alzheimer’s disease
title_fullStr Neuromorphic deviations associated with transcriptomic expression and specific cell type in Alzheimer’s disease
title_full_unstemmed Neuromorphic deviations associated with transcriptomic expression and specific cell type in Alzheimer’s disease
title_short Neuromorphic deviations associated with transcriptomic expression and specific cell type in Alzheimer’s disease
title_sort neuromorphic deviations associated with transcriptomic expression and specific cell type in alzheimer s disease
topic Alzheimer’s disease
Cognitive decline
Cell types
Morphometric similarity network
Gene expression
url https://doi.org/10.1038/s41598-025-90872-w
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