Characteristics of peripheral immune system in a novel <i>App^NL‐G‐F</i> knock‐in mouse model of Alzheimer’s disease

Background Increasing epidemiological, clinical, and experimental evidence suggests that Alzheimer’s disease (AD) pathogenesis is closely associated with systemic abnormalities, including dynamic processes in the peripheral immune compartment inflammation1,2,3. Recent reports transgenic AD animal models propose a role of dysregulated system memory impairment4,5. In this regard, contribution response driving different pathological stages less understood. Therefore, utilizing novel App knock-in mouse model (AppNL-G-F) exhibiting robust Aβ pathology, neuroinflammation impairment, we have explored relation pathology development brain alterations compartment. Method Using flowcytometry, characterized AppNL-G-F mice at (early-plaque: 3-month-old; plaque + early impairment: 7-month-old; late stages: 12-month-old) investigated distribution activation status various cells splenic primary cells. Result Among from innate immunity macrophages, natural killer dendritic cells, there was significant increase macrophage number mice. While percent B adaptive reduced (as observed patients2), no changes total T cell following 3, 7 12-months age compared to wild-type controls observed. showed examined by CD69 PD-L1 expression old subsets, CD4, CD8 regulatory (Treg) comparable control all groups. However, rise follicular helper (Tfh) 3-month age, altered molecule ICOS AppNL-G-Fmice. Conclusion These findings show reduction their during aggressive deposition brain, reflecting possible reinforcing importance further investigation. Our data suggest Tfh stage pathology. An may answer impaired protective antibody production reported AD6,7. The macrophages demands