Altered Blood and Brain Expression of Inflammation and Redox Genes in Alzheimer's Disease, Common to APP(V717I) x TAU(P301L) Mice and Patients

Despite intensive research, the pathophysiology of Alzheimer's disease (AD) is still not fully understood, and currently there are no effective treatments. Therefore, there is an unmet need for reliable biomarkers and animal models of AD to develop innovative therapeutic strategies addressing early pathologic events such as neuroinflammation and redox disturbances. The study aims to identify inflammatory and redox dysregulations in the context of AD-specific neuronal cell death and DNA damage, using the APP(V717I)x TAU(P301L) (AT) mouse model of AD. The expression of 84 inflammatory and 84 redox genes in the hippocampus and peripheral blood of double transgenic AT mice was evaluated against age-matched controls. A distinctive gene expression profile in the hippocampus and the blood of AT mice was identified, addressing DNA damage, apoptosis and thrombosis, complemented by inflammatory factors and receptors, along with ROS producers and antioxidants. Gene expression dysregulations that are common to AT mice and AD patients guided the final selection of candidate biomarkers. The identified inflammation and redox genes, common to AD patients and AT mice, might be valuable candidate biomarkers for preclinical drug development that could be readily translated to clinical trials.

Automated summary

This study aimed to identify inflammatory and redox dysregulations in the context of AD-specific neuronal cell death and DNA damage using the APP(V717I)xTAU(P301L) (AT) mouse model. By evaluating gene expression in the hippocampus and blood of AT mice, potential candidate biomarkers for preclinical drug development were identified. These findings may be valuable in translating research results into clinical trials.