Stress regulates Alzheimer's Disease progression via selective enrichment of CD8+ T cells

This study investigates stress's impact on Alzheimer's disease (AD) using male APP/PS1 transgenic mice. Negative stressors (chronic social defeat, restraint) and positive hedonia (environmental enrichment, EE) were applied. Stress worsens AD pathology, while EE slows progression. Brain RNA-seq reveals IL-6 and IL-10 as key stress-related AD regulators. Flow cytometry shows CD8+/CD4+ T cell ratio shifts in response to SE and EE. SE increases CD8+/CD4+ ratio, opposite in EE. Depletion and enrichment of CD8+ T cells both accelerate AD, indicating immune intervention's negative impact. Stress management and balanced immunity may aid AD therapy, highlighting novel potential treatment. Overall design: After behavioral testing and peripheral blood flow cytometry, mice were gas anesthetized with isoflurane. Anesthetized mouse was perfused systemically with 20 mL of ice-cold PBS transapically to ensure high cell viability. The abdominal cavity was opened and the splenectomy was performed for flow cytometry of splenocytes. Then the mouse brain was immediately removed. The posterior half of the left hemisphere was isolated and fixed in ice-cold 4% paraformaldehyde for overnight for immunofluorescence staining. The posterior half of the right hemisphere is used for lysing by RIPA lysate to extract brain proteins. The brain stem and the anterior half of the brain were used to extract RNA for RNA sequencing.