The impact of Alzheimer's disease on cortical complexity and its underlying biological mechanisms

Background: Alzheimer's disease (AD) might impact the complexity of cerebral cortex, and the underlying biological mechanisms responsible for cortical changes in the AD cortex remain unclear. Methods: Fifty-eight participants with AD and 67 normal controls underwent high-resolution 3 T structur...

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Main Authors: Leian Chen, Xiao Zhou, Yanan Qiao, Yu Wang, Zhi Zhou, Shuhong Jia, Yu Sun, Dantao Peng
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Brain Research Bulletin
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Online Access:http://www.sciencedirect.com/science/article/pii/S0361923025001327
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author Leian Chen
Xiao Zhou
Yanan Qiao
Yu Wang
Zhi Zhou
Shuhong Jia
Yu Sun
Dantao Peng
author_facet Leian Chen
Xiao Zhou
Yanan Qiao
Yu Wang
Zhi Zhou
Shuhong Jia
Yu Sun
Dantao Peng
author_sort Leian Chen
collection DOAJ
description Background: Alzheimer's disease (AD) might impact the complexity of cerebral cortex, and the underlying biological mechanisms responsible for cortical changes in the AD cortex remain unclear. Methods: Fifty-eight participants with AD and 67 normal controls underwent high-resolution 3 T structural brain MRI. Using surface-based morphometry (SBM), we created vertex-wise maps for group comparisons in terms of five measures: cortical thickness, fractal dimension, gyrification index, Toro’s gyrification index and sulcal depth respectively. Five machine learning (ML) models combining SBM parameters were established to predict AD. In addition, transcription–neuroimaging association analyses, as well as Mendelian randomization of AD and cortical thickness data, were conducted to investigate the genetic mechanisms and biological functions of AD. Results: AD patients exhibited topological changes in cortical complexity, with increased complexity in the frontal and temporal cortex and decreased complexity in the insula cortex, alongside extensive cortical atrophy. Combining different SBM measures could aid disease diagnosis. The genes involved in cell structure support and the immune response were the strongest contributors to cortical anatomical features in AD patients. The identified genes associated with AD cortical morphology were overexpressed or underexpressed in excitatory neurons, oligodendrocytes, and astrocytes. Conclusion: Complexity alterations of the cerebral surface may be associated with a range of biological processes and molecular mechanisms, including immune responses. The present findings may contribute to a more comprehensive understanding of brain morphological patterns in AD patients.
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spelling doaj-art-db19054b335c40e69209ce2e9fb5b9672025-08-20T02:19:19ZengElsevierBrain Research Bulletin1873-27472025-06-0122511132010.1016/j.brainresbull.2025.111320The impact of Alzheimer's disease on cortical complexity and its underlying biological mechanismsLeian Chen0Xiao Zhou1Yanan Qiao2Yu Wang3Zhi Zhou4Shuhong Jia5Yu Sun6Dantao Peng7China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Department of Neurology, China-Japan Friendship Hospital, Beijing, ChinaDepartment of Neurology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaDepartment of Neurology, China-Japan Friendship Hospital, Beijing, ChinaDepartment of Neurology, China-Japan Friendship Hospital, Beijing, ChinaDepartment of Neurology, China-Japan Friendship Hospital, Beijing, ChinaDepartment of Neurology, China-Japan Friendship Hospital, Beijing, ChinaDepartment of Neurology, China-Japan Friendship Hospital, Beijing, China; Corresponding author.China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Department of Neurology, China-Japan Friendship Hospital, Beijing, China; Corresponding author at: China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.Background: Alzheimer's disease (AD) might impact the complexity of cerebral cortex, and the underlying biological mechanisms responsible for cortical changes in the AD cortex remain unclear. Methods: Fifty-eight participants with AD and 67 normal controls underwent high-resolution 3 T structural brain MRI. Using surface-based morphometry (SBM), we created vertex-wise maps for group comparisons in terms of five measures: cortical thickness, fractal dimension, gyrification index, Toro’s gyrification index and sulcal depth respectively. Five machine learning (ML) models combining SBM parameters were established to predict AD. In addition, transcription–neuroimaging association analyses, as well as Mendelian randomization of AD and cortical thickness data, were conducted to investigate the genetic mechanisms and biological functions of AD. Results: AD patients exhibited topological changes in cortical complexity, with increased complexity in the frontal and temporal cortex and decreased complexity in the insula cortex, alongside extensive cortical atrophy. Combining different SBM measures could aid disease diagnosis. The genes involved in cell structure support and the immune response were the strongest contributors to cortical anatomical features in AD patients. The identified genes associated with AD cortical morphology were overexpressed or underexpressed in excitatory neurons, oligodendrocytes, and astrocytes. Conclusion: Complexity alterations of the cerebral surface may be associated with a range of biological processes and molecular mechanisms, including immune responses. The present findings may contribute to a more comprehensive understanding of brain morphological patterns in AD patients.http://www.sciencedirect.com/science/article/pii/S0361923025001327Alzheimer’s diseaseCortical complexitySurface-based morphometryMachine learningTranscription-neuroimaging association analysis
spellingShingle Leian Chen
Xiao Zhou
Yanan Qiao
Yu Wang
Zhi Zhou
Shuhong Jia
Yu Sun
Dantao Peng
The impact of Alzheimer's disease on cortical complexity and its underlying biological mechanisms
Brain Research Bulletin
Alzheimer’s disease
Cortical complexity
Surface-based morphometry
Machine learning
Transcription-neuroimaging association analysis
title The impact of Alzheimer's disease on cortical complexity and its underlying biological mechanisms
title_full The impact of Alzheimer's disease on cortical complexity and its underlying biological mechanisms
title_fullStr The impact of Alzheimer's disease on cortical complexity and its underlying biological mechanisms
title_full_unstemmed The impact of Alzheimer's disease on cortical complexity and its underlying biological mechanisms
title_short The impact of Alzheimer's disease on cortical complexity and its underlying biological mechanisms
title_sort impact of alzheimer s disease on cortical complexity and its underlying biological mechanisms
topic Alzheimer’s disease
Cortical complexity
Surface-based morphometry
Machine learning
Transcription-neuroimaging association analysis
url http://www.sciencedirect.com/science/article/pii/S0361923025001327
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