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Mol. Neurodegener., Jan 29 2025, 20 (1) 12 | https://doi.org/10.1186/s13024-025-00798-0
Cell-specific transcriptional signatures of vascular cells in Alzheimer's disease: perspectives, pathways, and therapeutic directions
Soumilee Chaudhuri1,2,3†, Minyoung Cho1,2,4†, Julia C. Stumpf5, Paula J. Bice1,2, Özkan İş8, Nilüfer Ertekin‑Taner8,9, Andrew J. Saykin1,2,6,7* and Kwangsik Nho1,2,7*
1Department of Radiology and Imaging Sciences, Center for Neuroimag‑ing, Indiana University School of Medicine, Indianapolis, IN, USA.
2Indiana Alzheimer’s Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA.
3Medical Neuroscience Graduate Program, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
4Department of Digital Health, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea.
5Ruth Lilly Medical Library Indiana University School of Medicine, Indianapolis, IN, USA.
6Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
7Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA.
8Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
9Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
†Soumilee Chaudhuri and Minyoung Cho contributed equally to this work.
*Correspondence: Andrew J. Saykin, Kwangsik Nho
1Department of Radiology and Imaging Sciences, Center for Neuroimag‑ing, Indiana University School of Medicine, Indianapolis, IN, USA.
2Indiana Alzheimer’s Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA.
3Medical Neuroscience Graduate Program, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
4Department of Digital Health, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea.
5Ruth Lilly Medical Library Indiana University School of Medicine, Indianapolis, IN, USA.
6Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
7Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA.
8Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
9Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
†Soumilee Chaudhuri and Minyoung Cho contributed equally to this work.
*Correspondence: Andrew J. Saykin, Kwangsik Nho
Abstract
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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- Review Paper
- 2025년 01월 (BRIC 등록일 2025-02-03)
- 국내+국외 연구진
- 생명과학 > 유전학
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