An Anti-β-Amyloid Vaccine for Treating Cognitive Deficits in a Mouse Model of Down Syndrome
| Autor: | Ann Becker, Lorianne Rey-Bellet, Andrea Pfeifer, Michael T. Maloney, Pavel V. Belichenko, Anne Granet, Dorin Mlaki, Valérie Giriens, Sara K. Bengtsson, David T. Hickman, Andreas Muhs, Rime Madani, Adeline Plassard, Nishant Singhal, Rachel L. Nosheny, Maria Pihlgren, Long Do, Stephanie Vuillermot, Gordon R. Linke, Matthew L. Pearn, Janice S. Valletta, William C. Mobley, Pedro Reis, María Pilar López-Deber, Alexander M. Kleschevnikov, Eliezer Masliah |
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| Přispěvatelé: | Herault, Yann |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
Aging medicine.medical_treatment Alzheimer's Disease Biochemistry Transgenic Mice 0302 clinical medicine Amyloid precursor protein Public and Occupational Health Aetiology Enzyme-Linked Immunoassays lcsh:Science Mammals Basal forebrain Behavior Animal Vaccination Brain Cholinergic Neurons 3. Good health Blood Neurology Amyloid Intellectual and Developmental Disabilities (IDD) Immunology Hemorrhage 03 medical and health sciences Alzheimer Disease Memory Cholinergic neuron Immunoassays Behavior Animal lcsh:R Organisms Biology and Life Sciences Proteins medicine.disease Prevention of disease and conditions 030104 developmental biology lcsh:Q Dementia Preventive Medicine Atrophy Down Syndrome Cognition Disorders 030217 neurology & neurosurgery Biomarkers 0301 basic medicine and promotion of well-being Physiology lcsh:Medicine Monophosphoryl Lipid A Neurodegenerative Immune Physiology Medicine and Health Sciences 2.1 Biological and endogenous factors Vaccines Multidisciplinary Immune System Proteins biology Neurodegenerative Diseases Animal Models Hematology Vaccination and Immunization Body Fluids 3.4 Vaccines Neurological Vertebrates Anatomy Adjuvant Research Article Down syndrome General Science & Technology Mouse Models Mice Transgenic Research and Analysis Methods Rodents Antibodies Blood Plasma Vaccine Related Model Organisms mental disorders Mental Health and Psychiatry medicine Acquired Cognitive Impairment Animals Inflammation Amyloid beta-Peptides business.industry Neurosciences Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) Newborn Brain Disorders Disease Models Animal Good Health and Well Being Animals Newborn Gene Expression Regulation Disease Models Amniotes biology.protein Immunologic Techniques Immunization Septal Nuclei business |
| Zdroj: | PLoS ONE PloS one, vol 11, iss 3 PLoS ONE, Vol 11, Iss 3, p e0152471 (2016) |
| ISSN: | 1932-6203 |
| Popis: | In Down syndrome (DS) or trisomy of chromosome 21, the β-amyloid (Aβ) peptide product of the amyloid precursor protein (APP) is present in excess. Evidence points to increased APP gene dose and Aβ as playing a critical role in cognitive difficulties experienced by people with DS. Particularly, Aβ is linked to the late-life emergence of dementia as associated with neuropathological markers of Alzheimer's disease (AD). At present, no treatment targets Aβ-related pathogenesis in people with DS. Herein we used a vaccine containing the Aβ 1-15 peptide embedded into liposomes together with the adjuvant monophosphoryl lipid A (MPLA). Ts65Dn mice, a model of DS, were immunized with the anti-Aβ vaccine at 5 months of age and were examined for cognitive measures at 8 months of age. The status of basal forebrain cholinergic neurons and brain levels of APP and its proteolytic products were measured. Immunization of Ts65Dn mice resulted in robust anti-Aβ IgG titers, demonstrating the ability of the vaccine to break self-tolerance. The vaccine-induced antibodies reacted with Aβ without detectable binding to either APP or its C-terminal fragments. Vaccination of Ts65Dn mice resulted in a modest, but non-significant reduction in brain Aβ levels relative to vehicle-treated Ts65Dn mice, resulting in similar levels of Aβ as diploid (2N) mice. Importantly, vaccinated Ts65Dn mice showed resolution of memory deficits in the novel object recognition and contextual fear conditioning tests, as well as reduction of cholinergic neuron atrophy. No treatment adverse effects were observed; vaccine did not result in inflammation, cellular infiltration, or hemorrhage. These data are the first to show that an anti-Aβ immunotherapeutic approach may act to target Aβ-related pathology in a mouse model of DS. |
| Databáze: | OpenAIRE |
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