p38α‐MAPK‐deficient myeloid cells ameliorate symptoms and pathology of APP‐transgenic Alzheimer's disease mice

• DOI: 10.1111/acel.13679
• Publication Date: 2022-08-01T05:54:40Z
• Authors: Qinghua Luo; Laura Schnöder; Wenlin Hao; Kathrin Litzenburger; Yann Decker; Inge Tomic; Michael D. Menger; Yang Liu; Klaus Fassbender
• Keywords: 0301 basic medicine; ddc:610; Amyloid beta-Peptides; Interleukin-17; amyloid-beta (Aβ); neurodegeneration; 610; microglia; Mice, Transgenic; Alzheimer's disease; 3. Good health; Mice, Inbred C57BL; Mitogen-Activated Protein Kinase 14; Amyloid beta-Protein Precursor; Disease Models, Animal; Mice; 03 medical and health sciences; Alzheimer Disease; Animals; Myeloid Cells; p38α-MAPK; Microglia; Research Articles

Alzheimer's disease (AD), the most common cause of dementia in elderly, is pathologically characterized by extracellular deposition amyloid-β peptides (Aβ) and microglia-dominated inflammatory activation brain. p38α-MAPK activated both neurons microglia. How microglia contributes to AD pathogenesis remains unclear. In this study, we conditionally knocked out all myeloid cells or specifically APP-transgenic mice, examined animals for AD-associated pathologies (i.e., cognitive deficits, Aβ pathology, neuroinflammation) individual their internalization at different stages (e.g., 4 9 months age). Our experiments showed that p38α-MAPK-deficient were more effective than reducing cerebral neuronal impairment mice. Deficiency inhibited but enhanced it months. Inflammatory promoted microglial Aβ. Interestingly, reduced IL-17a-expressing CD4-positive lymphocytes not 4-month-old By cross-breeding mice with Il-17a-knockout observed IL-17a deficiency potentially brain as shown 9-month-old Thus, cells, only microglia, prevents progression. may partially mediate pathogenic role peripheral cells. study supports a therapeutic target patients.