Altered Intersubject Variability of Morphological Connectivity in Cerebral Small Vessel Disease and Its Associations With Gene Expression and Cell Types
6 affiliations
- 1The Second Affiliated Hospital of Anhui Medical University
- 2The First Affiliated Hospital of Anhui Medical University
- 3Anhui Medical University
- 4Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders
- 5Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health
- 6the Second Affiliated Hospital of Anhui Medical University
Abstract
BACKGROUND: Cerebral small vessel disease (CSVD) is a heterogeneous disorder; however, interindividual variability in morphometric brain connectivity remains unclear, as does its association with gene expression. METHODS: We enrolled 65 patients with CSVD and 35 healthy controls. Individual-level morphometric brain networks were constructed from T1-weighted magnetic resonance imaging, and intersubject variability of morphometric connectivity (IVMC) was quantified using a Kullback-Leibler divergence-based gray matter similarity measure. Group differences in IVMC and its associations with cognitive and clinical measures were examined. Partial least squares regression was applied to Allen Human Brain Atlas data to relate IVMC to gene expression, cell-type specificity, and biological functions. RESULTS: <0.05). IVMC in the sensorimotor and ventral attention networks was associated with poorer Auditory-Verbal Learning Test performance. Partial least squares regression analysis revealed that IVMC-related genes were enriched in neurodevelopmental and metabolic processes, whereas negatively weighted genes were associated with synaptic structure and glutamatergic signaling. Cell-type analyses linked IVMC alterations primarily to neuronal and glial transcriptional signatures. CONCLUSIONS: CSVD is associated with elevated IVMC across multiple functional networks, with changes in specific networks linked to memory impairment. These alterations may be associated with genes involved in neurodevelopment, synaptic function, and diverse neuronal and glial cell types, providing new insights into the interindividual variability of brain networks and the neurophysiological mechanisms underlying CSVD.
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BibTeX
@article{hu2026altered,
title = {{Altered Intersubject Variability of Morphological Connectivity in Cerebral Small Vessel Disease and Its Associations With Gene Expression and Cell Types}},
author = {Jie Hu and Xin Wang and Siyu Fan and Wei Wang and Jianru Sun and Xiaohui Xie and Fengbo Xing and Dai Zhang and Qiang Wei and Xiaokun Qi and Yanghua Tian and Jun Zhang},
journal = {Journal of the American Heart Association},
year = {2026},
month = oct,
doi = {10.1161/jaha.126.049778},
url = {https://www.ahajournals.org/doi/10.1161/JAHA.126.049778},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Altered Intersubject Variability of Morphological Connectivity in Cerebral Small Vessel Disease and Its Associations With Gene Expression and Cell Types
AU - Jie Hu
AU - Xin Wang
AU - Siyu Fan
AU - Wei Wang
AU - Jianru Sun
AU - Xiaohui Xie
AU - Fengbo Xing
AU - Dai Zhang
AU - Qiang Wei
AU - Xiaokun Qi
AU - Yanghua Tian
AU - Jun Zhang
PY - 2026
DA - 2026/10/20
JO - Journal of the American Heart Association
DO - 10.1161/jaha.126.049778
UR - https://www.ahajournals.org/doi/10.1161/JAHA.126.049778
AB - BACKGROUND: Cerebral small vessel disease (CSVD) is a heterogeneous disorder; however, interindividual variability in morphometric brain connectivity remains unclear, as does its association with gene expression. METHODS: We enrolled 65 patients with CSVD and 35 healthy controls. Individual-level morphometric brain networks were constructed from T1-weighted magnetic resonance imaging, and intersubject variability of morphometric connectivity (IVMC) was quantified using a Kullback-Leibler divergence-based gray matter similarity measure. Group differences in IVMC and its associations with cognitive and clinical measures were examined. Partial least squares regression was applied to Allen Human Brain Atlas data to relate IVMC to gene expression, cell-type specificity, and biological functions. RESULTS: <0.05). IVMC in the sensorimotor and ventral attention networks was associated with poorer Auditory-Verbal Learning Test performance. Partial least squares regression analysis revealed that IVMC-related genes were enriched in neurodevelopmental and metabolic processes, whereas negatively weighted genes were associated with synaptic structure and glutamatergic signaling. Cell-type analyses linked IVMC alterations primarily to neuronal and glial transcriptional signatures. CONCLUSIONS: CSVD is associated with elevated IVMC across multiple functional networks, with changes in specific networks linked to memory impairment. These alterations may be associated with genes involved in neurodevelopment, synaptic function, and diverse neuronal and glial cell types, providing new insights into the interindividual variability of brain networks and the neurophysiological mechanisms underlying CSVD.
SN - 2047-9980
ER -