Blood genome-wide gene expression microarray profiles in female patients with advanced Alzheimer's Disease and healthy controls

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 ECM 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. Study subjects were all female, including patients with advanced AD (n=9, age 79.3±12.3 years) and age–matched female healthy controls (n=10, age 72.1±13.1 years). Peripheral blood from each study subjects were processed to isolate RNA. The isolated blood RNAs were assayed byt geneome-wide gene expression microarrays using the Sureprint G3 Human Gene Expression 8x60k v2 microarrays (Agilent Technologies, CA)