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Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer’s disease

Chen, S; Chang, Y; Li, L; Acosta, D; Li, Y; Guo, Q; Wang, C; ... Fu, H; + view all (2022) Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer’s disease. Acta Neuropathologica Communications , 10 (1) , Article 188. 10.1186/s40478-022-01494-6. Green open access

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Abstract

Human middle temporal gyrus (MTG) is a vulnerable brain region in early Alzheimer’s disease (AD), but little is known about the molecular mechanisms underlying this regional vulnerability. Here we utilize the 10 × Visium platform to define the spatial transcriptomic profile in both AD and control (CT) MTG. We identify unique marker genes for cortical layers and the white matter, and layer-specific differentially expressed genes (DEGs) in human AD compared to CT. Deconvolution of the Visium spots showcases the significant difference in particular cell types among cortical layers and the white matter. Gene co-expression analyses reveal eight gene modules, four of which have significantly altered co-expression patterns in the presence of AD pathology. The co-expression patterns of hub genes and enriched pathways in the presence of AD pathology indicate an important role of cell–cell-communications among microglia, oligodendrocytes, astrocytes, and neurons, which may contribute to the cellular and regional vulnerability in early AD. Using single-molecule fluorescent in situ hybridization, we validated the cell-type-specific expression of three novel DEGs (e.g., KIF5A, PAQR6, and SLC1A3) and eleven previously reported DEGs associated with AD pathology (i.e., amyloid beta plaques and intraneuronal neurofibrillary tangles or neuropil threads) at the single cell level. Our results may contribute to the understanding of the complex architecture and neuronal and glial response to AD pathology of this vulnerable brain region.

Type: Article
Title: Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer’s disease
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s40478-022-01494-6
Publisher version: https://doi.org/10.1186/s40478-022-01494-6
Language: English
Additional information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Keywords: Alzheimer’s disease, Astrocytes, Human middle temporal gyrus, Microglia, Neurons, Oligodendrocytes, Single-molecule fluorescent in situ hybridization, Spatially resolved transcriptomics, Vulnerability, Weighted gene co-expression network analyses (WGCNA), Humans, Alzheimer Disease, Transcriptome, Amyloid beta-Peptides, In Situ Hybridization, Fluorescence, Temporal Lobe, Kinesins
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > UK Dementia Research Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10162674
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