Back to Search
Start Over
Active vaccination with ankyrin G reduces β-amyloid pathology in APP transgenic mice.
- Source :
-
Molecular psychiatry [Mol Psychiatry] 2013 Mar; Vol. 18 (3), pp. 358-68. Date of Electronic Publication: 2012 Jun 12. - Publication Year :
- 2013
-
Abstract
- Serum antibodies against amyloid-β peptide (Aβ) in humans with or without diagnosis of Alzheimer's disease (AD) indicate the possibility of immune responses against brain antigens. In an unbiased screening for antibodies directed against brain proteins, we found in AD patients high serum levels of antibodies against the neuronal cytoskeletal protein ankyrin G (ankG); these correlated with slower rates of cognitive decline. Neuronal expression of ankG was higher in AD brains than in nondemented age-matched healthy control subjects. AnkG was present in exosomal vesicles, and it accumulated in β-amyloid plaques. Active immunization with ankG of arcAβ transgenic mice reduced brain β-amyloid pathology and increased brain levels of soluble Aβ(42). AnkG immunization induced a reduction in β-amyloid pathology, also in Swedish transgenic mice(.) Anti-ankG monoclonal antibodies reduced Aβ-induced loss of dendritic spines in hippocampal ArcAβ organotypic cultures. Together, these data established a role for ankG in the human adaptive immune response against resident brain proteins, and they show that ankG immunization reduces brain β-amyloid and its related neuropathology.
- Subjects :
- Alzheimer Disease blood
Alzheimer Disease pathology
Amyloid beta-Peptides antagonists & inhibitors
Amyloid beta-Peptides metabolism
Amyloid beta-Peptides toxicity
Animals
Ankyrins metabolism
Antibodies blood
Antibodies, Monoclonal pharmacology
Brain metabolism
Cells, Cultured
Hippocampus cytology
Hippocampus drug effects
Humans
Mice
Mice, Transgenic
Neurons cytology
Peptide Fragments metabolism
Plaque, Amyloid metabolism
Alzheimer Disease immunology
Alzheimer Disease prevention & control
Ankyrins immunology
Brain pathology
Vaccination
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5578
- Volume :
- 18
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecular psychiatry
- Publication Type :
- Academic Journal
- Accession number :
- 22688190
- Full Text :
- https://doi.org/10.1038/mp.2012.70