@article{0363b89add8b4a6ab189da9953b17044,
title = "ESHRD: Deconvolution of brain homogenate rna expression data to identify novel cell-type-specific alterations in Alzheimer's disease",
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.",
keywords = "Brain homogenates, Endothelial cells, Laser capture microdissection, Oligodendrocytes, RNA sequencing",
author = "Piras, {Ignazio S.} and Christiane Bleul and Talboom, {Joshua S.} and {De Both}, {Matthew D.} and Isabelle Schrauwen and Glenda Halliday and Myers, {Amanda J.} and Serrano, {Geidy E.} and Beach, {Thomas G.} and Huentelman, {Matthew J.}",
note = "Funding Information: The authors acknowledge funding support from NIH-NIA grant R01-AG041232 (Multiple-PI; to Matthew Huentelman and Amanda Myers) and the State of Arizona DHS (Arizona Alzheimer's Consortium, PI; Eric Reiman). The MSA laser capture microdissection work was supported by NIH-NINDS grant R21-NS093222 to Matthew Huentelman. All of the Alzheimer's Disease RNA sequencing data used for this study were downloaded from the AMP-AD portal (Accession number: Syn14237651). Mayo Study: Study data were provided by the following sources: The Mayo Clinic Alzheimers Disease Genetic Studies, led by Dr. Nilufer Taner and Dr. Steven G. Younkin, Mayo Clinic, Jacksonville, FL using samples from the Mayo Clinic Study of Aging, the Mayo Clinic Alzheimers Disease Research Center, and the Mayo Clinic Brain Bank. Data collection was supported through funding by NIA grants P50 AG016574, R01 AG032990, U01 AG046139, R01 AG018023, U01 AG006576, U01 AG006786, R01 AG025711, R01 AG017216, R01 AG003949, NINDS grant R01 NS080820, CurePSP Foundation, and support from Mayo Foundation. Study data includes samples collected through the Sun Health Research Institute Brain and Body Donation Program of Sun City, Arizona, and the New South Wales (NSW) Brain Bank (Sydney, AU). The Brain and Body Donation Program www.aging-us.com 4134 AGING is supported by the National Institute of Neurological Disorders and Stroke (U24 NS072026 National Brain and Tissue Resource for Parkinsons Disease and Related Disorders), the National Institute on Aging (P30 AG19610 Arizona Alzheimers Disease Core Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimers Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901 and 1001 to the Arizona Parkinson's Disease Consortium) and the Michael J. Fox Foundation for Parkinsons Research. ROSMAP study: Gene Expression data from this study was funded by grant U01AG046152. Mount Sinai Study: Gene Expression data for this study was funded through grant U01AG046170.",
year = "2020",
month = mar,
day = "15",
doi = "10.18632/aging.102840",
language = "English (US)",
volume = "12",
pages = "4124--4162",
journal = "Aging",
issn = "1945-4589",
publisher = "US Administration on Aging",
number = "5",
}