Identifying Blood Transcriptome Biomarkers of Alzheimer's Disease Using Transgenic Mice

The testing of pathological biomarkers of Alzheimer's disease (AD), such as amyloid beta and tau, is time-consuming, expensive, and invasive. Here, we used 3xTg-AD mice to identify and validate putative novel blood transcriptome biomarkers of AD that can potentially be identified in the blood of patients. mRNA was extracted from the blood and hippocampus of 3xTg-AD and control mice at different ages and used for microarray analysis. Network and functional analyses revealed that the differentially expressed genes between AD and control mice modulated the immune and neuroinflammation systems. Five novel gene transcripts (Cdkn2a,Apobec3,Magi2,Parp3, andCass4) showed significant increases with age, and their expression in the blood was collated with that in the hippocampus only in AD mice. We further assessed previously identified candidate biomarker genes. The expression ofTrem1andTrem2in both the blood and brain was significantly increased with age. DecreasedTomm40and increasedPink1mRNA levels were observed in the mouse blood. The changes in the expression ofSncaandApoe mRNAin the mouse blood and brain were similar to those found in human AD blood. Our results demonstrated that the immune and neuroinflammatory system is involved in the pathophysiologies of aging and AD and that the blood transcriptome might be useful as a biomarker of AD.