Browsing by Author "Cho, Minyoung"

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    Cell-specific transcriptional signatures of vascular cells in Alzheimer’s disease: perspectives, pathways, and therapeutic directions
    (Springer Nature, 2025-01-29) Chaudhuri, Soumilee; Cho, Minyoung; Stumpff, Julia C.; Bice, Paula J; İş, Özkan; Ertekin-Taner, Nilüfer; Saykin, Andrew J.; Nho, Kwangsik
    Alzheimer’s disease (AD) is a debilitating neurodegenerative disease that is marked by profound neurovascular dysfunction and significant cell-specific alterations in the brain vasculature. Recent advances in high throughput single-cell transcriptomics technology have enabled the study of the human brain vasculature at an unprecedented depth. Additionally, the understudied niche of cerebrovascular cells, such as endothelial and mural cells, and their subtypes have been scrutinized for understanding cellular and transcriptional heterogeneity in AD. Here, we provide an overview of rich transcriptional signatures derived from recent single-cell and single-nucleus transcriptomic studies of human brain vascular cells and their implications for targeted therapy for AD. We conducted an in-depth literature search using Medline and Covidence to identify pertinent AD studies that utilized single-cell technologies in human post-mortem brain tissue by focusing on understanding the transcriptional differences in cerebrovascular cell types and subtypes in AD and cognitively normal older adults. We also discuss impaired cellular crosstalk between vascular cells and neuroglial units, as well as astrocytes in AD. Additionally, we contextualize the findings from single-cell studies of distinct endothelial cells, smooth muscle cells, fibroblasts, and pericytes in the human AD brain and highlight pathways for potential therapeutic interventions as a concerted multi-omic effort with spatial transcriptomics technology, neuroimaging, and neuropathology. Overall, we provide a detailed account of the vascular cell-specific transcriptional signatures in AD and their crucial cellular crosstalk with the neuroglial unit.
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    Functional insight into East Asian-specific genetic risk loci for Alzheimer's disease
    (Wiley, 2025) Cho, Minyoung; Chaudhuri, Soumilee; Liu, Shiwei; Park, Tamina; Huang, Yen-Ning; Rosewood, Thea; Bice, Paula J.; Saykin, Andrew J.; Won, Hong-Hee; Nho, Kwangsik; Radiology and Imaging Sciences, School of Medicine
    Introduction: The functional study of genetic risk factors for Alzheimer's disease (AD) provides insights into the underlying mechanisms and identification of potential therapeutic targets. Investigating AD-associated genetic loci identified in East Asian populations using single-nucleus RNA-sequencing data may identify novel functional genetic contributors. Methods: Cell type-specific expression quantitative trait loci (eQTL) and peak-to-gene links were used to identify functional genes associated with 26 genetic loci from seven genome-wide association studies (GWAS) for AD in East Asians. Results: KCNJ6 and MAPK1IP1L were identified as significant eQTLs with AD risk loci. AD risk loci were in peaks related to four genes, with CLIC4 being connected across different cell types. Genes identified in European and East Asian GWAS interacted within networks and were enriched in AD pathology pathways in astrocytes. Discussion: Our findings suggest KCNJ6 and CLIC4 as novel AD-associated functional genes, providing insight into the genetic architecture of AD in East Asians. Highlights: Integrated functional analysis of Alzheimer's disease (AD) loci in seven East Asian genome-wide association studies (GWAS) was performed. Cell type-specific expression quantitative trait loci (eQTLs) and assay for transposase-accessible chromatin peaks were used to identify AD functional genes. An AD risk variant was linked to KCNJ6 through an oligodendrocyte progenitor cell-specific eQTL. An AD risk variant maps to open chromatin, linked to CLIC4 across six cell types. Astrocyte differentially expressed genes by AD pathology are enriched in East Asian and European GWAS genes.
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    Whole-genome sequencing analyses suggest novel genetic factors associated with Alzheimer’s disease and a cumulative effects model for risk liability
    (Springer Nature, 2025-05-26) Kim, Jun Pyo; Cho, Minyoung; Kim, Chanhee; Lee, Hyunwoo; Jang, Beomjin; Jung, Sang-Hyuk; Kim, Yujin; Koh, In Gyeong; Kim, Seoyeon; Shin, Daeun; Lee, Eun Hye; Lee, Jong-Young; Park, YoungChan; Jang, Hyemin; Kim, Bo-Hyun; Ham, Hongki; Kim, Beomsu; Kim, Yujin; Cho, A-Hyun; Raj, Towfique; Kim, Hee Jin; Na, Duk L.; Seo, Sang Won; An, Joon-Yong; Won, Hong-Hee; Radiology and Imaging Sciences, School of Medicine
    Genome-wide association studies (GWAS) on Alzheimer's disease (AD) have predominantly focused on identifying common variants in Europeans. Here, we performed whole-genome sequencing (WGS) of 1,559 individuals from a Korean AD cohort to identify various genetic variants and biomarkers associated with AD. Our GWAS analysis identified a previously unreported locus for common variants (APCDD1) associated with AD. Our WGS analysis was extended to explore the less-characterized genetic factors contributing to AD risk. We identified rare noncoding variants located in cis-regulatory elements specific to excitatory neurons associated with cognitive impairment. Moreover, structural variation analysis showed that short tandem repeat expansion was associated with an increased risk of AD, and copy number variant at the HPSE2 locus showed borderline statistical significance. APOE ε4 carriers with high polygenic burden or structural variants exhibited severe cognitive impairment and increased amyloid beta levels, suggesting a cumulative effects model of AD risk.