Whole Blood Expression Pattern of Inflammation and Redox Genes in Mild Alzheimer's Disease.

BACKGROUND

Although Alzheimer's disease (AD) is associated with alterations of the central nervous system, this disease has an echo in blood that might represent a valuable source of biomarkers for improved diagnosis, prognosis and for monitoring drug response.

METHODS

We performed a targeted transcriptomics study on 38 mild Alzheimer's disease (AD) patients and 38 matched controls for evaluating the expression levels of 136 inflammation and 84 redox genes in whole blood. Patients were diagnosed as mild AD based on altered levels of total TAU, phospho-TAU and Abeta in cerebrospinal fluid, and Abeta, Abeta and total TAU levels in plasma. Whenever possible, blood and brain comparisons were made using public datasets.

RESULTS

We found 48 inflammation and 34 redox genes differentially expressed in the blood of AD patients vs controls (FC >1.5, p < 0.01), out of which 22 pro-inflammatory and 12 redox genes exhibited FC >2 and p < 0.001. Receiver operating characteristic (ROC) analysis identified nine inflammation and seven redox genes that discriminated between AD patients and controls (area under the curve >0.9). Correlations of the dysregulated inflammation and redox transcripts indicated that may regulate several redox genes including and . Based on the gene expression profile, we have found that the master regulators of inflammation and redox homeostasis, NFκB and NRF2, were significantly disturbed in the blood of AD patients, as well as several zinc finger and helix-loop-helix transcription factors.

CONCLUSION

The selected inflammation and redox genes might be useful biomarkers for monitoring anti-inflammatory therapy in mild AD.