Single-cell spatial proteomic imaging for human neuropathology

• DOI: 10.1186/s40478-022-01465-x
• Publication Date: 2022-11-04T20:19:11Z
• Authors: Kausalia Vijayara...; Bryan J. Cannon; Dmitry Tebaykin; Marc Bossé; Alex Baranski; J. P. Oliveria; Syed A. Bukhari; Dunja Mrdjen; M. Ryan Corces; Erin F. McCaffrey; Noah F. Greenwald; Yari Sigal; Diana Marquez; Zumana Khair; Trevor Bruce; Mako Goldston; Anusha Bharadwaj; Kathleen S. Montine; R. Michael Angelo; Thomas J. Montine; Sean C. Bendall
• Keywords: Neuropathology; Human brain

Abstract Neurodegenerative disorders are characterized by phenotypic changes and hallmark proteopathies. Quantifying these in archival human brain tissues remains indispensable for validating animal models understanding disease mechanisms. We present a framework nanometer-scale, spatial proteomics with multiplex ion beam imaging (MIBI) capturing neuropathological features. MIBI facilitated simultaneous, quantitative of 36 proteins on hippocampus from individuals spanning cognitively normal to dementia. Customized analysis strategies identified cell types proteopathies the across stages Alzheimer’s (AD) neuropathologic change. show microglia-pathologic tau interactions hippocampal CA1 subfield AD Data driven, sample independent creation proteomic regions persistent neurons pathologic neighborhoods expressing mitochondrial protein MFN2, regardless cognitive status, suggesting survival advantage. Our study revealed unique insights multiplexed data-driven approaches serves broadly as methodology neuropathology. Teaser Multiplex Ion Imaging enables deep phenotyping neuropathology-associated cellular