Back to Search
Start Over
Naturally occurring autoantibodies against Aβ oligomers exhibited more beneficial effects in the treatment of mouse model of Alzheimer's disease than intravenous immunoglobulin
- Source :
- Neuropharmacology. 105:561-576
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Alzheimer's disease (AD) is characterized by memory loss, intracellular neurofibrillary tangles, and extracellular plaque deposits composed of β-amyloid (Aβ). Previous reports showed that naturally occurring autoantibodies, such as intravenous immunoglobulin (IVIG), benefited patients with moderate-stage AD who carried an APOE-ε4 allele. However, the mechanism underlying the role of IVIG remains unclear. In this study, we identified naturally occurring autoantibodies against Aβ oligomers (NAbs-Aβo), which were purified by Aβ42 oligomer or Cibacron Blue affinity chromatography from IVIG and termed as Oli-NAbs and Blue-NAbs, respectively. Oli-NAbs and Blue-NAbs recognized Aβ42 oligomers or both Aβ40 and 42 oligomers, differently. Both antibodies inhibited Aβ42 aggregation and attenuated Aβ42-induced cytotoxicity. Compared with vehicles, Oli-NAbs, Blue-NAbs and IVIG significantly improved the memory and cognition, and reduced the soluble and oligomeric Aβ levels in APPswe/PS1dE9 transgenic mice. Further investigation showed that Blue-NAbs at increased doses effectively decreased plaque burden and insoluble Aβ levels, whereas Oli-NAbs significantly declined the microgliosis and astrogliosis, as well as the production of proinflammatory cytokines in vivo. Therefore, high levels of these antibodies against oligomeric Aβ40 or Aβ42 were required, correspondingly, to achieve the optimal effect. NAbs-Aβo could be condensed to a high concentration by affinity chromatography and its isolation from IVIG may not interfere with the normal function of conventional IVIG as its concentration is very low. Thus, the isolated NAbs-Aβo as an extra product of plasma required low cost and the enriched NAbs-Aβo may be more feasible than IVIG for the treatment of AD.
- Subjects :
- 0301 basic medicine
Genetically modified mouse
Neuroimmunomodulation
Synaptophysin
Mice, Transgenic
Pharmacology
Chromatography, Affinity
Proinflammatory cytokine
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Affinity chromatography
Alzheimer Disease
Memory
Cell Line, Tumor
hemic and lymphatic diseases
medicine
Extracellular
Animals
Humans
Gliosis
Nootropic Agents
Autoantibodies
Amyloid beta-Peptides
biology
Chemistry
Autoantibody
Brain
Immunoglobulins, Intravenous
medicine.disease
Peptide Fragments
Astrogliosis
Disease Models, Animal
Neuroprotective Agents
030104 developmental biology
Immunology
biology.protein
Cytokines
Immunotherapy
Protein Multimerization
Alzheimer's disease
Antibody
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 00283908
- Volume :
- 105
- Database :
- OpenAIRE
- Journal :
- Neuropharmacology
- Accession number :
- edsair.doi.dedup.....9d5a6ffb0fb54c026c4311a53e9408ad
- Full Text :
- https://doi.org/10.1016/j.neuropharm.2016.02.015