Abstract
Background: Soluble oligomeric amyloid-β (Aβ), rather than Aβ plaques, seems to be the culprit in Alzheimer's disease (AD). Accordingly, a new concept vaccine of small cyclic peptide conjugates, selectively targeting oligomeric Aβ, has been developed.
Objective: Study the therapeutic potential of this new vaccine in a mouse model for AD.
Methods: J20 mice, overexpressing human amyloid precursor protein, were validated for an AD-like phenotype. Then, J20 mice were vaccinated at 2, 3, and 4 months of age and AD phenotype was evaluated at 6, 9, and 12 months of age; or at 9, 10, and 11 months with evaluation at 12 months. Effects on Aβ pathology were studied by plaque load (immunohistochemistry; 6E10) and antibody titers against Aβ (ELISA). AD behavioral phenotype was evaluated by performance in a battery of cognitive tests.
Results: J20 mice displayed age-related Aβ plaque development and an AD-like behavioral phenotype. A consistent antibody response to the cyclic peptides was, however, not extended to Aβ, leaving plaque load unaffected. Nevertheless, immunization at young ages prevented working- and short-term spatial memory loss, but deteriorated long-term spatial learning and memory, at 12 months of age. Immunization at later ages did not affect any measured parameter.
Conclusion: J20 mice provide a relevant model for AD to study potential anti-Aβ treatment. Early vaccination prevented short-term memory loss at later ages, but deteriorated long-term spatial memory, however without affecting Aβ pathology. Later vaccination had no effects, but optimal timing may require further investigation.
Original language | English |
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Pages (from-to) | 261-280 |
Number of pages | 20 |
Journal | Journal of Alzheimer’s Disease |
Volume | 4 |
Issue number | 1 |
DOIs | |
Publication status | Published - 23-Jul-2020 |
Keywords
- Alzheimer's disease
- amyloid-beta
- cognition
- vaccine
- MOUSE MODEL
- SYNAPTIC PLASTICITY
- IMMUNIZATION
- DEPOSITION
- BRAIN
- HIPPOCAMPAL
- IMPAIRMENT
- MICROGLIA
- PLAQUES
- AN1792