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Proteomic analysis across patient iPSC-based models and human post-mortem hippocampal tissue reveals early cellular dysfunction and progression of Alzheimer's disease pathogenesis

Pomeshchik, Yuriy LU orcid ; Velasquez, Erika LU ; Gil, Jeovanis LU orcid ; Klementieva, Oxana LU orcid ; Gidlöf, Ritha LU ; Sydoff, Marie LU ; Bagnoli, Silvia ; Nacmias, Benedetta ; Sorbi, Sandro and Westergren-Thorsson, Gunilla LU orcid , et al. (2023) In Acta Neuropathologica Communications 11.
Abstract

The hippocampus is a primary region affected in Alzheimer's disease (AD). Because AD postmortem brain tissue is not available prior to symptomatic stage, we lack understanding of early cellular pathogenic mechanisms. To address this issue, we examined the cellular origin and progression of AD pathogenesis by comparing patient-based model systems including iPSC-derived brain cells transplanted into the mouse brain hippocampus. Proteomic analysis of the graft enabled the identification of pathways and network dysfunction in AD patient brain cells, associated with increased levels of Aβ-42 and β-sheet structures. Interestingly, the host cells surrounding the AD graft also presented alterations in cellular biological pathways. Furthermore,... (More)

The hippocampus is a primary region affected in Alzheimer's disease (AD). Because AD postmortem brain tissue is not available prior to symptomatic stage, we lack understanding of early cellular pathogenic mechanisms. To address this issue, we examined the cellular origin and progression of AD pathogenesis by comparing patient-based model systems including iPSC-derived brain cells transplanted into the mouse brain hippocampus. Proteomic analysis of the graft enabled the identification of pathways and network dysfunction in AD patient brain cells, associated with increased levels of Aβ-42 and β-sheet structures. Interestingly, the host cells surrounding the AD graft also presented alterations in cellular biological pathways. Furthermore, proteomic analysis across human iPSC-based models and human post-mortem hippocampal tissue projected coherent longitudinal cellular changes indicative of early to end stage AD cellular pathogenesis. Our data showcase patient-based models to study the cell autonomous origin and progression of AD pathogenesis.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Mice, Humans, Alzheimer Disease, Induced Pluripotent Stem Cells, Proteomics, Autopsy, Hippocampus
in
Acta Neuropathologica Communications
volume
11
article number
150
publisher
BioMed Central (BMC)
external identifiers
  • pmid:37715247
  • scopus:85171384157
ISSN
2051-5960
DOI
10.1186/s40478-023-01649-z
language
English
LU publication?
yes
additional info
© 2023. BioMed Central Ltd., part of Springer Nature.
id
652ae1e0-7bc4-4bfa-8109-3292ab279715
date added to LUP
2023-09-23 20:01:02
date last changed
2024-11-30 01:16:26
@article{652ae1e0-7bc4-4bfa-8109-3292ab279715,
  abstract     = {{<p>The hippocampus is a primary region affected in Alzheimer's disease (AD). Because AD postmortem brain tissue is not available prior to symptomatic stage, we lack understanding of early cellular pathogenic mechanisms. To address this issue, we examined the cellular origin and progression of AD pathogenesis by comparing patient-based model systems including iPSC-derived brain cells transplanted into the mouse brain hippocampus. Proteomic analysis of the graft enabled the identification of pathways and network dysfunction in AD patient brain cells, associated with increased levels of Aβ-42 and β-sheet structures. Interestingly, the host cells surrounding the AD graft also presented alterations in cellular biological pathways. Furthermore, proteomic analysis across human iPSC-based models and human post-mortem hippocampal tissue projected coherent longitudinal cellular changes indicative of early to end stage AD cellular pathogenesis. Our data showcase patient-based models to study the cell autonomous origin and progression of AD pathogenesis.</p>}},
  author       = {{Pomeshchik, Yuriy and Velasquez, Erika and Gil, Jeovanis and Klementieva, Oxana and Gidlöf, Ritha and Sydoff, Marie and Bagnoli, Silvia and Nacmias, Benedetta and Sorbi, Sandro and Westergren-Thorsson, Gunilla and Gouras, Gunnar K and Rezeli, Melinda and Roybon, Laurent}},
  issn         = {{2051-5960}},
  keywords     = {{Animals; Mice; Humans; Alzheimer Disease; Induced Pluripotent Stem Cells; Proteomics; Autopsy; Hippocampus}},
  language     = {{eng}},
  month        = {{09}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Acta Neuropathologica Communications}},
  title        = {{Proteomic analysis across patient iPSC-based models and human post-mortem hippocampal tissue reveals early cellular dysfunction and progression of Alzheimer's disease pathogenesis}},
  url          = {{http://dx.doi.org/10.1186/s40478-023-01649-z}},
  doi          = {{10.1186/s40478-023-01649-z}},
  volume       = {{11}},
  year         = {{2023}},
}