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Spatial and single-nucleus transcriptomic analysis of genetic and sporadic forms of Alzheimer's Disease.
Miyoshi, Emily; Morabito, Samuel; Henningfield, Caden M; Rahimzadeh, Negin; Kiani Shabestari, Sepideh; Das, Sudeshna; Michael, Neethu; Reese, Fairlie; Shi, Zechuan; Cao, Zhenkun; Scarfone, Vanessa; Arreola, Miguel A; Lu, Jackie; Wright, Sierra; Silva, Justine; Leavy, Kelsey; Lott, Ira T; Doran, Eric; Yong, William H; Shahin, Saba; Perez-Rosendahl, Mari; Head, Elizabeth; Green, Kim N; Swarup, Vivek.
Afiliación
  • Miyoshi E; Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA.
  • Morabito S; Institute for Memory Impairments and Neurological Disorders (MIND), University of California Irvine, Irvine, CA, USA.
  • Henningfield CM; Institute for Memory Impairments and Neurological Disorders (MIND), University of California Irvine, Irvine, CA, USA.
  • Rahimzadeh N; Mathematical, Computational, and Systems Biology (MCSB) Program, University of California Irvine, Irvine, CA, USA.
  • Kiani Shabestari S; Center for Complex Biological Systems (CCBS), University of California Irvine, Irvine, CA, USA.
  • Das S; Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA.
  • Michael N; Institute for Memory Impairments and Neurological Disorders (MIND), University of California Irvine, Irvine, CA, USA.
  • Reese F; Institute for Memory Impairments and Neurological Disorders (MIND), University of California Irvine, Irvine, CA, USA.
  • Shi Z; Mathematical, Computational, and Systems Biology (MCSB) Program, University of California Irvine, Irvine, CA, USA.
  • Cao Z; Center for Complex Biological Systems (CCBS), University of California Irvine, Irvine, CA, USA.
  • Scarfone V; Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA.
  • Arreola MA; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA, USA.
  • Lu J; Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA.
  • Wright S; Institute for Memory Impairments and Neurological Disorders (MIND), University of California Irvine, Irvine, CA, USA.
  • Silva J; Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA.
  • Leavy K; Institute for Memory Impairments and Neurological Disorders (MIND), University of California Irvine, Irvine, CA, USA.
  • Lott IT; Center for Complex Biological Systems (CCBS), University of California Irvine, Irvine, CA, USA.
  • Doran E; Department of Developmental and Cell Biology, University of California Irvine, Irvine, CA, USA.
  • Yong WH; Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA.
  • Shahin S; Institute for Memory Impairments and Neurological Disorders (MIND), University of California Irvine, Irvine, CA, USA.
  • Perez-Rosendahl M; Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA.
  • Head E; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA, USA.
  • Green KN; Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA.
  • Swarup V; Institute for Memory Impairments and Neurological Disorders (MIND), University of California Irvine, Irvine, CA, USA.
bioRxiv ; 2023 Jul 26.
Article en En | MEDLINE | ID: mdl-37546983
ABSTRACT
The pathogenesis of Alzheimer's disease (AD) depends on environmental and heritable factors, with remarkable differences evident between individuals at the molecular level. Here we present a transcriptomic survey of AD using spatial transcriptomics (ST) and single-nucleus RNA-seq in cortical samples from early-stage AD, late-stage AD, and AD in Down Syndrome (AD in DS) donors. Studying AD in DS provides an opportunity to enhance our understanding of the AD transcriptome, potentially bridging the gap between genetic mouse models and sporadic AD. Our analysis revealed spatial and cell-type specific changes in disease, with broad similarities in these changes between sAD and AD in DS. We performed additional ST experiments in a disease timecourse of 5xFAD and wildtype mice to facilitate cross-species comparisons. Finally, amyloid plaque and fibril imaging in the same tissue samples used for ST enabled us to directly link changes in gene expression with accumulation and spread of pathology.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: BioRxiv Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: BioRxiv Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos