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Single-cell spatial proteomic imaging for human neuropathology.
Vijayaragavan, Kausalia; Cannon, Bryan J; Tebaykin, Dmitry; Bossé, Marc; Baranski, Alex; Oliveria, J P; Bukhari, Syed A; Mrdjen, Dunja; Corces, M Ryan; McCaffrey, Erin F; Greenwald, Noah F; Sigal, Yari; Marquez, Diana; Khair, Zumana; Bruce, Trevor; Goldston, Mako; Bharadwaj, Anusha; Montine, Kathleen S; Angelo, R Michael; Montine, Thomas J; Bendall, Sean C.
Afiliação
  • Vijayaragavan K; Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Cannon BJ; Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Tebaykin D; Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Bossé M; Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Baranski A; Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Oliveria JP; Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Bukhari SA; Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Mrdjen D; Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Corces MR; The Gladstone Institutes, San Francisco, CA, USA.
  • McCaffrey EF; Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Greenwald NF; Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Sigal Y; Ionpath, Inc, Menlo Park, CA, USA.
  • Marquez D; Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Khair Z; Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Bruce T; Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Goldston M; Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Bharadwaj A; Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Montine KS; Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Angelo RM; Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Montine TJ; Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Bendall SC; Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA. bendall@stanford.edu.
Acta Neuropathol Commun ; 10(1): 158, 2022 11 04.
Article em En | MEDLINE | ID: mdl-36333818
ABSTRACT
Neurodegenerative disorders are characterized by phenotypic changes and hallmark proteopathies. Quantifying these in archival human brain tissues remains indispensable for validating animal models and understanding disease mechanisms. We present a framework for nanometer-scale, spatial proteomics with multiplex ion beam imaging (MIBI) for capturing neuropathological features. MIBI facilitated simultaneous, quantitative imaging of 36 proteins on archival human hippocampus from individuals spanning cognitively normal to dementia. Customized analysis strategies identified cell types and proteopathies in the hippocampus across stages of Alzheimer's disease (AD) neuropathologic change. We show microglia-pathologic tau interactions in hippocampal CA1 subfield in AD dementia. Data driven, sample independent creation of spatial proteomic regions identified persistent neurons in pathologic tau neighborhoods expressing mitochondrial protein MFN2, regardless of cognitive status, suggesting a survival advantage. Our study revealed unique insights from multiplexed imaging and data-driven approaches for neuropathologic analysis and serves broadly as a methodology for spatial proteomic analysis of archival human neuropathology. TEASER Multiplex Ion beam Imaging enables deep spatial phenotyping of human neuropathology-associated cellular and disease features.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteômica / Doença de Alzheimer Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteômica / Doença de Alzheimer Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article