# Peripheral Oxidation-Inflammation and Immunosenescence in Triple-Transgenic Mice for Alzheimer’s Disease (3xTg-AD) at Early Neuropathological Stages of Disease and Decrease of Immune Impairment by Voluntary Exercise

## TL;DR

This study shows that immune and oxidative stress issues appear early in a mouse model of Alzheimer's disease and that exercise can help improve these issues.

## Contribution

The study reveals sex-independent immune impairment in 3xTg-AD mice at early disease stages and demonstrates that voluntary exercise mitigates immune dysfunction.

## Key findings

- 3xTg-AD mice show immune dysfunction and oxidative stress at 9 months, before major brain pathology.
- Voluntary exercise improves immune function in 3xTg-AD mice.
- Immune impairments in 3xTg-AD mice are similar in both sexes at early disease stages.

## Abstract

Inflammatory-oxidative stress generated by immune cells plays an important role in aging and in age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Triple-transgenic mice for AD (3xTg-AD) are a suitable model for mimicking this disease in an age-dependent manner. We previously showed that peritoneal leukocyte functions and their redox-inflammatory state are altered early in female 3xTg-AD mice, which exhibit premature aging compared to non-transgenic (NTg) animals. However, their characteristics at 9 months of age, when they present an early neuropathological state, and the sex differences are not known. Here, we analyzed several spleen and thymus leukocyte functions (chemotaxis, natural killer activity, and lymphoproliferation in response to mitogens), pro-inflammatory (IL-1B, TNF-alpha) and anti-inflammatory (IL-10) released cytokine concentrations, and redox parameters (glutathione concentrations and glutathione peroxidase, glutathione reductase, and xanthine oxidase activities) in male and female 3xTg-AD mice compared to age-matched controls. We also analyzed the effects of voluntary physical exercise on immune functions. Our results show that 9-month-old male and female 3xTg-AD mice have worse immune functions, redox state, and inflammation than NTg counterparts. Physical exercise improves immune function. Thus, accelerated aging reflected by peripheral immunosenescence and oxidation-inflammation in 3xTg-AD mice precedes hallmark neuropathology, and exercise can slow down AD progression.