title: Function and redox state of peritoneal leukocytes as preclinical and prodromic markers in a longitudinal study of triple-transgenic mice for Alzheimer's disease.
abstract: The aging process involves the impairment of the immune system (immunosenescence), based on the imbalance of the redox status, as occurs in neurodegenerative diseases such as Alzheimer's disease (AD). Since in AD there is a systemic disorder, we aimed to assess longitudinally, from before the onset until the complete establishment of AD, cell populations, several functions, and oxidative stress parameters in peritoneal leukocytes of triple transgenic mice for AD (3xTgAD). These animals mimic the human AD pathophysiology. The results indicate a premature immunosenescence in 3xTgAD at 4 months of age, when the immunoreactivity against intracellular amyloid-β fibrils appears. Thus, decreases in functions such as chemotaxis, phagocytosis, and lymphoproliferation, as well as a lower reduced glutathione content and higher xanthine oxidase activity, appear in leukocytes. Moreover, NK percentage and cytotoxic activity, CD25+ B and naïve CD8 T cells percentage, GSSG/GSH ratio, and GSH content were already changed before the onset of AD, at the age of 2 months. Furthermore, the changes in some parameters such as CD5+ B1 cells, phagocytosis, lymphoproliferation, and xanthine oxidase activity continue at 15 months of age, when AD pathophysiology is completely established. Because the immune system parameters studied are markers of health and longevity, the premature immunosenescence could explain the shorter life span shown by 3xTgAD observed in the present work. These results suggest that peripheral immune cell functions and their oxidative stress status could be good early peripheral markers of the preclinical and prodromal stages and progression of AD.
authors: Department of Physiology (Animal Physiology II), Faculty of Biology, Complutense University of Madrid (UCM), Madrid, Spain.
authors: Ianire
authors: I
authors: Maté
authors: Department of Physiology (Animal Physiology II), Faculty of Biology, Complutense University of Madrid (UCM), Madrid, Spain.
authors: Julia
authors: J
authors: Cruces
authors: Department of Psychiatry and Forensic Medicine and Institute of Neuroscince, Faculty of Medicine, Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain.
authors: Lydia
authors: L
authors: Giménez-Llort
authors: Department of Physiology (Animal Physiology II), Faculty of Biology, Complutense University of Madrid (UCM), Madrid, Spain.
authors: Mónica
authors: M
authors: De la Fuente
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology* / Q000401:mortality; D000818:Animals; D002374:Catalase / Q000378:metabolism; D049109:Cell Proliferation / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology*; D008137:Longitudinal Studies; D008264:Macrophages / Q000502:physiology; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010084:Oxidation-Reduction; D010529:Peritoneal Cavity; D010587:Phagocytosis / Q000502:physiology; D062706:Prodromal Symptoms; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D002374:Catalase; D014969:Xanthine Oxidase; D005978:Glutathione
keywords: 3xTgAD; Immune function; immunosenescence; oxidative stress; peritoneal leukocytes