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

Autor:	Oberman K; Department of Neurobiology GELIFES, University Groningen, The Netherlands., Gouweleeuw L; Department of Neurobiology GELIFES, University Groningen, The Netherlands., Hoogerhout P; INTRAVACC, Bilthoven, The Netherlands., Eisel ULM; Department of Neurobiology GELIFES, University Groningen, The Netherlands., van Riet E; INTRAVACC, Bilthoven, The Netherlands., Schoemaker RG; Department of Neurobiology GELIFES, University Groningen, The Netherlands.; University Medical Center Groningen, The Netherlands.
Jazyk:	angličtina
Zdroj:	Journal of Alzheimer's disease reports [J Alzheimers Dis Rep] 2020 Jul 23; Vol. 4 (1), pp. 261-280. Date of Electronic Publication: 2020 Jul 23.
DOI:	10.3233/ADR-200213
Abstrakt:	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. Competing Interests: The authors have no conflict of interest to report. (© 2020 – IOS Press and the authors. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu