Imaging patterns and genetic associations of brain atrophy across distinct symptom stages in Parkinson's disease.
Imaging patterns and genetic associations of brain atrophy across distinct symptom stages in Parkinson's disease.
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CN · Author affiliation · country only
Department of Radiology The Affiliated Wuxi People's Hospital of Nanjing Medical University Wuxi Jiangsu China.Location evidence
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Original abstract
BACKGROUND: Parkinson's disease (PD) involves progressive gray matter (GM) atrophy, but stage-specific imaging patterns and their genetic mechanisms remain unclear. This study aimed to characterize GM atrophy across PD stages and link these patterns to transcriptional profiles. METHODS: A total of 542 patients with PD were obtained from the Parkinson's Progression Markers Initiative (PPMI) database, including early-stage (<2.5 years, n = 192), mid-stage (2.5-5.0 years, n = 235), and late-stage (>5.0 years, n = 115). Structural magnetic resonance imaging data underwent voxel-based morphometry analysis and group differences were assessed using voxel-wise two-sample t-tests with age, sex, and total intracranial volume as covariates, followed by correlation analyses between significant GM clusters and clinical features. Gene expression data from Allen Human Brain Atlas (http://www.brain-map.org) were spatially mapped to imaging patterns with gene-wise Pearson's correlations, as well as a series of enrichment, tissue-specific, and disease-association analyses. RESULTS: Compared to early-stage PD, the mid-stage showed brain GM atrophy in brain regions such as the right angular gyrus, superior temporal gyrus, and middle frontal gyrus (p < 0.05, cluster-level FWE correction). As PD progressed to the late stage, GM atrophy expanded to the left angular gyrus, left temporal pole, middle occipital gyrus, and bilateral posterior cingulate gyrus (p < 0.05, cluster-level FWE correction). Transcriptomic analyses identified 1262 shared genes across all stages, 1222 early-mid-stage-specific genes, and 1847 mid-late-stage-specific genes (p < 0.05, FWE correction). Gene enrichment analysis showed that the three gene sets shared 13 cellular components and 10 biological processes that were enriched in common expression pathways, presenting both shared and specific functional changes at different stages of PD progression. CONCLUSION: Progressive GM atrophy in PD reflects coordinated but stage-differentiated molecular processes, revealing cellular and genetic architectures underlying disease progression.