An Anti-β-Amyloid Vaccine for Treating Cognitive Deficits in a Mouse Model of Down Syndrome
| العنوان: | An Anti-β-Amyloid Vaccine for Treating Cognitive Deficits in a Mouse Model of Down Syndrome |
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| المؤلفون: | 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 |
| المساهمون: | Herault, Yann |
| المصدر: | PLoS ONE PloS one, vol 11, iss 3 PLoS ONE, Vol 11, Iss 3, p e0152471 (2016) |
| بيانات النشر: | Public Library of Science, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0dfba69d0dfcfb75e94cc602c199ebe4Test http://europepmc.org/articles/PMC4811554Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0dfba69d0dfcfb75e94cc602c199ebe4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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