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Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease

Chen, W-T; Lu, A; Craessaerts, K; Pavie, B; Sala Frigerio, C; Corthout, N; Qian, X; ... De Strooper, B; + view all (2020) Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease. Cell , 182 (4) 976-991.e19. 10.1016/j.cell.2020.06.038. Green open access

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Abstract

Although complex inflammatory-like alterations are observed around the amyloid plaques of Alzheimer's disease (AD), little is known about the molecular changes and cellular interactions that characterize this response. We investigate here, in an AD mouse model, the transcriptional changes occurring in tissue domains in a 100-μm diameter around amyloid plaques using spatial transcriptomics. We demonstrate early alterations in a gene co-expression network enriched for myelin and oligodendrocyte genes (OLIGs), whereas a multicellular gene co-expression network of plaque-induced genes (PIGs) involving the complement system, oxidative stress, lysosomes, and inflammation is prominent in the later phase of the disease. We confirm the majority of the observed alterations at the cellular level using in situ sequencing on mouse and human brain sections. Genome-wide spatial transcriptomics analysis provides an unprecedented approach to untangle the dysregulated cellular network in the vicinity of pathogenic hallmarks of AD and other brain diseases.

Type: Article
Title: Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cell.2020.06.038
Publisher version: https://doi.org/10.1016/j.cell.2020.06.038
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Alzheimer’s disease, amyloid plaque, astrocyte, cellular phase, complement cascade, in situ sequencing, microglia, myelination, oligodendrocyte, spatial transcriptomics
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
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UK Dementia Research Institute HQ
URI: https://discovery.ucl.ac.uk/id/eprint/10107515
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