ESHRD: Deconvolution of brain homogenate rna expression data to identify novel cell-type-specific alterations in Alzheimer's disease

Ignazio S. Piras, Christiane Bleul, Joshua S. Talboom, Matthew D. De Both, Isabelle Schrauwen, Glenda Halliday, Amanda J. Myers, Geidy E. Serrano, Thomas G. Beach, Matthew J. Huentelman

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Objective: We describe herein a bioinformatics approach that leverages gene expression data from brain homogenates to derive cell-type specific differential expression results. Results: We found that differentially expressed (DE) cell-specific genes were mostly identified as neuronal, microglial, or endothelial in origin. However, a large proportion (75.7%) was not attributable to specific cells due to the heterogeneity in expression among brain cell types. Neuronal DE genes were consistently downregulated and associated with synaptic and neuronal processes as described previously in the field thereby validating this approach. We detected several DE genes related to angiogenesis (endothelial cells) and proteoglycans (oligodendrocytes). Conclusions: We present a cost-and time-effective method exploiting brain homogenate DE data to obtain insights about cell-specific expression. Using this approach we identify novel findings in AD in endothelial cells and oligodendrocytes that were previously not reported. Methods: We derived an enrichment score for each gene using a publicly available RNA profiling database generated from seven different cell types isolated from mouse cerebral cortex. We then classified the differential expression results from 3 publicly accessible Late-Onset Alzheimer's disease (AD) studies including seven different brain regions.

Original languageEnglish (US)
Pages (from-to)4124-4162
Number of pages39
JournalAging
Volume12
Issue number5
DOIs
StatePublished - Mar 15 2020
Externally publishedYes

Keywords

  • Brain homogenates
  • Endothelial cells
  • Laser capture microdissection
  • Oligodendrocytes
  • RNA sequencing

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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    Piras, I. S., Bleul, C., Talboom, J. S., De Both, M. D., Schrauwen, I., Halliday, G., Myers, A. J., Serrano, G. E., Beach, T. G., & Huentelman, M. J. (2020). ESHRD: Deconvolution of brain homogenate rna expression data to identify novel cell-type-specific alterations in Alzheimer's disease. Aging, 12(5), 4124-4162. https://doi.org/10.18632/aging.102840