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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.
- Source :
-
Neurobiology of aging [Neurobiol Aging] 2015 Jan; Vol. 36 (1), pp. 111-22. Date of Electronic Publication: 2014 Jul 03. - Publication Year :
- 2015
-
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.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Alzheimer Disease prevention & control
Alzheimer Disease psychology
Animals
Brain metabolism
Injections, Intraperitoneal
Mice
Mice, Transgenic
Microglia immunology
Phagocytosis
Plaque, Amyloid immunology
Aging immunology
Alzheimer Disease immunology
Alzheimer Disease therapy
Amyloid beta-Peptides immunology
Bone Marrow Cells cytology
Bone Marrow Cells immunology
Dendritic Cells transplantation
Immunotherapy methods
Peptide Fragments immunology
Spleen cytology
Spleen transplantation
Subjects
Details
- Language :
- English
- ISSN :
- 1558-1497
- Volume :
- 36
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Neurobiology of aging
- Publication Type :
- Academic Journal
- Accession number :
- 25085784
- Full Text :
- https://doi.org/10.1016/j.neurobiolaging.2014.06.029