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. 2022 May 21;23(10):5799.
doi: 10.3390/ijms23105799.

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

Catalina Anca Cucos  1 , Elena Milanesi  1 , Maria Dobre  1 , Ioana Andreea Musat  2 , Gina Manda  1 , Antonio Cuadrado  1   3   4   5   6
Affiliations

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

Catalina Anca Cucos et al. Int J Mol Sci. .

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.

Keywords: Alzheimer’s disease; blood; gene expression; hippocampus; inflammation; redox alterations.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Heat maps of individual gene expression data in the hippocampus of 10 transgenic AT mice and 8 WT controls (A) and in the whole blood of 9 AT mice and 7 WT controls (B). Genes with |FR| > 1.5 and p < 0.05 in AT mice vs. WT controls are shown. Data are presented as 2−ΔCT values and are scaled considering the highest value as 100%. Genes that are over-expressed in AT mice appear in dark tones in this group and in lighter tones in the control group. Genes that are under-expressed in AT mice appear in dark tones in the control group and lighter tones in diseased mice. NFkB target genes are marked with *, while redox-responsive genes are marked with #.
Figure 2
Figure 2
Inflammation and redox-related genes that are differentially expressed in the hippocampus of AT mice (N = 10) vs. WT mice (N = 8), exhibiting |FR| values > 1.8. Data are presented as 2−∆CT values, and lines represent the expression average ± standard error of the mean (SEM). Comparisons between mice groups were made using the Mann–Whitney U-test, and differences were considered significant for p < 0.05.
Figure 2
Figure 2
Inflammation and redox-related genes that are differentially expressed in the hippocampus of AT mice (N = 10) vs. WT mice (N = 8), exhibiting |FR| values > 1.8. Data are presented as 2−∆CT values, and lines represent the expression average ± standard error of the mean (SEM). Comparisons between mice groups were made using the Mann–Whitney U-test, and differences were considered significant for p < 0.05.
Figure 3
Figure 3
Inflammation and redox-related genes differentially expressed in the whole blood of AT mice (N = 9) vs. WT mice (N = 7), exhibiting |FR| values > 1.8. Data are presented as 2−∆CT values, and lines represent the expression average ± standard error of the mean (SEM). Comparisons between mice groups were made using the Mann–Whitney U-test, and differences were considered significant for p < 0.05.
Figure 3
Figure 3
Inflammation and redox-related genes differentially expressed in the whole blood of AT mice (N = 9) vs. WT mice (N = 7), exhibiting |FR| values > 1.8. Data are presented as 2−∆CT values, and lines represent the expression average ± standard error of the mean (SEM). Comparisons between mice groups were made using the Mann–Whitney U-test, and differences were considered significant for p < 0.05.
Figure 4
Figure 4
Inflammation and redox-related genes differentially and commonly expressed in the hippocampus and in the whole blood of AT mice vs. WT controls. Only genes with |FR| > 1.8 and p < 0.05 are reported. Red font indicates up-regulated and green font down-regulated genes.
Figure 5
Figure 5
Correlations between the mRNA hippocampal levels of (A) inflammation and (B) redox genes with the age (in weeks) of AT mice (N = 10). Genes with |FR| > 1.8 and p < 0.05 were analyzed. The gene expression levels are presented as 2−∆CT values.
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