title: Blood genome-wide transcriptional profiles reflect broad molecular impairments and strong blood-brain links in Alzheimer's disease.
abstract: To date, little is known regarding the etiology and disease mechanisms of Alzheimer's disease (AD). There is a general urgency for novel approaches to advance AD research. In this study, we analyzed blood RNA from female patients with advanced AD and matched healthy controls using genome-wide gene expression microarrays. Our data showed significant alterations in 3,944 genes (≥2-fold, FDR ≤1%) in AD whole blood, including 2,932 genes that are involved in broad biological functions. Importantly, we observed abnormal transcripts of numerous tissue-specific genes in AD blood involving virtually all tissues, especially the brain. Of altered genes, 157 are known to be essential in neurological functions, such as neuronal plasticity, synaptic transmission and neurogenesis. More importantly, 205 dysregulated genes in AD blood have been linked to neurological disease, including AD/dementia and Parkinson's disease, and 43 are known to be the causative genes of 42 inherited mental retardation and neurodegenerative diseases. The detected transcriptional abnormalities also support robust inflammation, profound extracellular matrix impairments, broad metabolic dysfunction, aberrant oxidative stress, DNA damage, and cell death. While the mechanisms are currently unclear, this study demonstrates strong blood-brain correlations in AD. The blood transcriptional profiles reflect the complex neuropathological status in AD, including neuropathological changes and broad somatic impairments. The majority of genes altered in AD blood have not previously been linked to AD. We believe that blood genome-wide transcriptional profiling may provide a powerful and minimally invasive tool for the identification of novel targets beyond Aβ and tauopathy for AD research.
authors: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors: Bartholomew J
authors: BJ
authors: Naughton
authors: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors: F Jason
authors: FJ
authors: Duncan
authors: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors: Darren A
authors: DA
authors: Murrey
authors: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors: Aaron S
authors: AS
authors: Meadows
authors: Biomedical Genomics Core, Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors: David E
authors: DE
authors: Newsom
authors: Division of Cognitive Neurology, Forest Hills Center for Alzheimer's Disease, College of Medicine and Public Health, The Ohio State University, Columbus, OH, USA Department of Neurology, College of Medicine and Public Health, The Ohio State University, Columbus, OH, USA.
authors: Nicoleta
authors: N
authors: Stoicea
authors: Biomedical Genomics Core, Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA Department of Pediatrics, College of Medicine and Public Health, The Ohio State University, Columbus, OH, USA.
authors: Peter
authors: P
authors: White
authors: Division of Cognitive Neurology, Forest Hills Center for Alzheimer's Disease, College of Medicine and Public Health, The Ohio State University, Columbus, OH, USA Department of Neurology, College of Medicine and Public Health, The Ohio State University, Columbus, OH, USA.
authors: Douglas W
authors: DW
authors: Scharre
authors: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA Department of Pediatrics, College of Medicine and Public Health, The Ohio State University, Columbus, OH, USA.
authors: Douglas M
authors: DM
authors: Mccarty
authors: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA Department of Pediatrics, College of Medicine and Public Health, The Ohio State University, Columbus, OH, USA.
authors: Haiyan
authors: H
authors: Fu
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D046228:Microarray Analysis; D060888:Real-Time Polymerase Chain Reaction
keywords: Alzheimer's disease; blood-brain transcriptional association; genome-wide expression arrays; neuropathology