Vaccination prevented short-term memory loss, but deteriorated long-term spatial memory in Alzheimer's disease mice, independent of amyloid-β pathology

Klaske Oberman, Leonie Gouweleeuw, Peter Hoogerhout, Ulrich L M Eisel, Elly van Riet, Regien G Schoemaker*

*Bijbehorende auteur voor dit werk

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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.

Originele taal-2English
Pagina's (van-tot)261-280
Aantal pagina's20
TijdschriftJournal of Alzheimer’s Disease
Nummer van het tijdschrift1
StatusPublished - 23-jul-2020

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