Immunization with Small Amyloid-ß-derived Cyclopeptide Conjugates Diminishes Amyloid-ß-Induced Neurodegeneration in Mice.
J Alzheimers Dis
; 52(3): 1111-23, 2016.
Article
em En
| MEDLINE
| ID: mdl-27060957
ABSTRACT
BACKGROUND:
Soluble oligomeric (misfolded) species of amyloid-ß (Aß) are the main mediators of toxicity in Alzheimer's disease (AD). These oligomers subsequently form aggregates of insoluble fibrils that precipitate as extracellular and perivascular plaques in the brain. Active immunization against Aß is a promising disease modifying strategy. However, eliciting an immune response against Aß in general may interfere with its biological function and was shown to cause unwanted side-effects. Therefore, we have developed a novel experimental vaccine based on conformational neo-epitopes that are exposed in the misfolded oligomeric Aß, inducing a specific antibody response.OBJECTIVE:
Here we investigate the protective effects of the experimental vaccine against oligomeric Aß1-42-induced neuronal fiber loss in vivo.METHODS:
C57BL/6 mice were immunized or mock-immunized. Antibody responses were measured by enzyme-linked immunosorbent assay. Next, mice received a stereotactic injection of oligomeric Aß1-42 into the nucleus basalis of Meynert (NBM) on one side of the brain (lesion side), and scrambled Aß1-42 peptide in the contralateral NBM (control side). The densities of choline acetyltransferase-stained cholinergic fibers origination from the NBM were measured in the parietal neocortex postmortem. The percentage of fiber loss in the lesion side was determined relative to the control side of the brain.RESULTS:
Immunized responders (79%) showed 23% less cholinergic fiber loss (pâ=â0.01) relative to mock-immunized mice. Moreover, fiber loss in immunized responders correlated negatively with the measured antibody responses (R2â=â0.29, pâ=â0.02).CONCLUSION:
These results may provide a lead towards a (prophylactic) vaccine to prevent or at least attenuate (early onset) AD symptoms.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Peptídeos Cíclicos
/
Peptídeos beta-Amiloides
/
Imunização
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Doenças Neurodegenerativas
Limite:
Animals
Idioma:
En
Revista:
J Alzheimers Dis
Assunto da revista:
GERIATRIA
/
NEUROLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Holanda