Spatially Resolved Transcriptomics Reveals Gene Signatures Underlying the Vulnerability of Human Middle Temporal Gyrus in Alzheimer's Disease
Year: 2021
Type: preprint
Study design: Observational Study
Abstract: Human middle temporal gyrus (MTG) is a vulnerable brain region in early Alzheimer's disease (AD); however, little is known about the molecular mechanisms underlying this regional vulnerability. Here we use the 10x Visium platform to define the spatial topography of gene expression in the MTG from both early AD and control cases. We identify differentially expressed genes (DEGs) and enriched pathways that may contribute to the layer-specific vulnerability of AD pathology. Also, gene co-expression analyses reveal four gene modules, which significantly change their co-expression patterns in the presence of variations of AD pathology. Furthermore, we validate the changes of key representative DEGs that are associated with AD pathology using single-molecule fluorescent in situ hybridization. In summary, we provide a rich resource for the spatial transcriptomic profile of the human MTG, which will contribute to our understanding of the complex architecture and AD pathology of this vulnerable brain region.
Source: SSRN Electronic Journal
DOI: 10.2139/ssrn.3898080
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: U.S. Department of Defense, Michael J. Fox Foundation for Parkinson's Research, Alzheimer's Association, Ohio State University, Arizona Department of Health Services, Nationwide Children's Hospital, University College London, Arizona Biomedical Research Commission, National Institutes of Health, National Institute on Aging, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke
Awards: G1052080286, G1858189645, G250893170, INVESTIGATING THE IMPACT OF BAG3 ON ALZHEIMER-LIKE PATHOLOGY AND COGNITIVE DEFICITS ASSOCIATED WITH TRAUMATIC BRAIN INJURY., G2898431357, G3228411741, G3250808129, G3310236632, G3521153818, G3540482749, The role of ectodermal-neural cortex 1 in selective neuronal vulnerability in aging and Alzheimer's disease, G3687506083, Identifying neurons vulnerable to tau pathology in early AD, G6030318873, G6125194395, G6138759730, Investigating the vulnerability of WFS1-expressing excitatory neurons to tau pathology in early Alzheimer's disease., Arizona Alzheimer's Disease Core Center, G7161884846, Construction of cell specific gene co-regulations signatures based on single cell transcriptomics analysis, G749472136, National Brain and Tissue Resource for Parkinson's Disease and Related Disorders, G7924111682, G837617365, G9000159448, Cancer Center Support Grant, G961669115
OpenAlex ID: W3193201016