Vaccination Prevented Short-Term Memory Loss, but Deteriorated Long-Term Spatial Memory in Alzheimer's Disease Mice, Independent of Amyloid-? Pathology.

ABSTRACT: Background:Soluble oligomeric amyloid-? (A?), rather than A? plaques, seems to be the culprit in Alzheimer's disease (AD). Accordingly, a new concept vaccine of small cyclic peptide conjugates, selectively targeting oligomeric A?, 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 A? pathology were studied by plaque load (immunohistochemistry; 6E10) and antibody titers against A? (ELISA). AD behavioral phenotype was evaluated by performance in a battery of cognitive tests. Results:J20 mice displayed age-related A? plaque development and an AD-like behavioral phenotype. A consistent antibody response to the cyclic peptides was, however, not extended to A?, 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-A? treatment. Early vaccination prevented short-term memory loss at later ages, but deteriorated long-term spatial memory, however without affecting A? pathology. Later vaccination had no effects, but optimal timing may require further investigation.

SUBMITTER: Oberman K 

PROVIDER: S-EPMC7458552 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature