title: Combined treatment of amyloid-β₁₋₄₂-stimulated bone marrow-derived dendritic cells plus splenocytes from young mice prevents the development of Alzheimer's disease in APPswe/PSENldE9 mice.
abstract: Anti-amyloid-β (Aβ) immunotherapy is a potential therapeutic strategy to reduce amyloid plaques and amyloid-associated pathologies in Alzheimer's disease (AD). Immune senescence with aging has also played a crucial role in AD pathogenesis and influences the effect of anti-Aβ immunotherapy. In this study, a combined treatment of Aβ₁₋₄₂-bone marrow-derived dendritic cells (BMDCs) with intraperitoneal injection of splenocytes from young mice was designed as a novel immunotherapy for AD in APPswe/PSEN1de9 transgenic mice models. The results showed that the combined treatment not only elevated the level of anti-Aβ antibodies but also reduced amyloid plaques in brain and finally ameliorated deterioration of spatial learning and memory in AD mice. Additionally, the results revealed an increase of CD68 positive microglial cells in the vicinity of amyloid plaques in the mouse brain, which was responsible for the enhanced phagocytosis of Aβ plaques. In conclusion, the Aβ₁₋₄₂-BMDCs plus splenocytes treatment improved the phagocytosis of microglia and prevented AD pathology more effectively. This combined immunotherapy provided a promising treatment in preventing the progression of AD in clinical studies in the near future.
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical College of Fudan University, Shanghai, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Radiology, Huashan Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Hanqiu
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical College of Fudan University, Shanghai, P.R. China.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Laboratory Animal Science, Fudan University, Shanghai, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ao
authors.affiliation: Department of Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Nick
authors.initials: N
authors.lastname: Moore
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical College of Fudan University, Shanghai, P.R. China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical College of Fudan University, Shanghai, P.R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical College of Fudan University, Shanghai, P.R. China.
authors.forename: Heng
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical College of Fudan University, Shanghai, P.R. China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical College of Fudan University, Shanghai, P.R. China.
authors.forename: Zixiao
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical College of Fudan University, Shanghai, P.R. China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Zhai
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical College of Fudan University, Shanghai, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical College of Fudan University, Shanghai, P.R. China.
authors.forename: Guomin
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical College of Fudan University, Shanghai, P.R. China.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Radiology, Huashan Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical College of Fudan University, Shanghai, P.R. China.
authors.forename: Ruixi
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical College of Fudan University, Shanghai, P.R. China. Electronic address: cmliang@fudan.edu.cn.
authors.forename: Chunmin
authors.initials: C
authors.lastname: Liang
mesh_terms: D000375:Aging / Q000276:immunology*; D000544:Alzheimer Disease / Q000276:immunology* / Q000517:prevention & control / Q000523:psychology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology*; D001921:Brain / Q000378:metabolism; D003713:Dendritic Cells / Q000637:transplantation*; D007167:Immunotherapy / Q000379:methods*; D007274:Injections, Intraperitoneal; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology*; D010587:Phagocytosis; D058225:Plaque, Amyloid / Q000276:immunology; D013154:Spleen / Q000166:cytology* / Q000637:transplantation*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's disease; Bone marrow derived dendritic cell; Immune senescence; Immunotherapy