Altered Blood and Brain Expression of Inflammation and Redox Genes in Alzheimer’s Disease, Common to APPV717I × TAUP301L Mice and Patients

Abstract

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 APPV717I× TAUP301L (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.

Evaluation of altered cell-cell communication between glia and neurons in the hippocampus of 3xTg-AD mice at two time points

“…73 However, previous work in the blood of a transgenic AD mouse model indicated increased expression of Card10 compared to WT mice. 74 Protein tyrosine phosphatase N22 (Ptpn22), an immune signaling regulator previously implicated in AD, 75,76 was the only other target gene that was significantly differentially expressed in both neuronal subpopulations at both time points (absolute log2FC > 0.2 with a Wald test padj < 0.05, Fig 4A & 4B). Target genes also showed changes in log2FC magnitude between 6 and 12 months (Table S6).…”