Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
Cognitive implications and associated transcriptomic signatures of distinct regional iron depositions in cerebral small vessel disease.
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Wang Youjie, Ye Chen, Pan Ruosu, Tang Biqiu, Li Congjun, Liu Junfeng, Tao Wendan, Zhang Xuening, Yang Tang, Yan Yuying, Jiang Shuai, Lui Su, Wu Bo
Аннотация
INTRODUCTION: Regional brain iron dyshomeostasis is observed in cerebral small vessel disease (cSVD) and other neurodegeneration processes. However, its spatial patterns, cognitive impact, and underlying pathological mechanisms remain unclear.
METHODS: Voxel-based analysis of quantitative susceptibility mapping (QSM) was used to detect regional susceptibility changes, and their correlations with cognitive function were assessed using linear regression. We combined the microarray dataset from the Allen Human Brain Atlas (AHBA) to explore the pathological mechanisms of iron deposition patterns.
RESULTS: A total of 87 cSVD patients and 80 controls were included in the study. Increased QSM values in the bilateral putamen and caudate were associated with cognitive decline in cSVD. Gene set enrichment analysis revealed the enrichment of gene sets related to central nervous system integrity.
DISCUSSION: Iron deposition in deep gray matter may indicate cognitive changes in cSVD and could be linked to the disruption of brain structural and functional integrity.
HIGHLIGHTS: Increased susceptibility values, indicating focal iron deposition, were observed in the deep gray matter of patients with cerebral small vessel disease (cSVD). Regional iron concentration in the deep gray nuclei was associated with cognitive impairment in cSVD patients. Imaging transcriptomics suggests that cSVD-related iron deposition is linked to the structural and functional integrity of the brain. An open-source script for imaging transcriptomics focusing on regional gene expression was developed and proposed.
METHODS: Voxel-based analysis of quantitative susceptibility mapping (QSM) was used to detect regional susceptibility changes, and their correlations with cognitive function were assessed using linear regression. We combined the microarray dataset from the Allen Human Brain Atlas (AHBA) to explore the pathological mechanisms of iron deposition patterns.
RESULTS: A total of 87 cSVD patients and 80 controls were included in the study. Increased QSM values in the bilateral putamen and caudate were associated with cognitive decline in cSVD. Gene set enrichment analysis revealed the enrichment of gene sets related to central nervous system integrity.
DISCUSSION: Iron deposition in deep gray matter may indicate cognitive changes in cSVD and could be linked to the disruption of brain structural and functional integrity.
HIGHLIGHTS: Increased susceptibility values, indicating focal iron deposition, were observed in the deep gray matter of patients with cerebral small vessel disease (cSVD). Regional iron concentration in the deep gray nuclei was associated with cognitive impairment in cSVD patients. Imaging transcriptomics suggests that cSVD-related iron deposition is linked to the structural and functional integrity of the brain. An open-source script for imaging transcriptomics focusing on regional gene expression was developed and proposed.