Abeta-specific T-cells reverse cognitive decline and synaptic loss in Alzheimer's mice
| Autor: | Chuanhai Cao, Gary W. Arendash, Daniel Shippy, Melissa Runfeldt, Douglas W. Ethell, Jennifer R. Cracchiolo, Brett Blake |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Genetically modified mouse
Adoptive cell transfer medicine.medical_treatment T-Lymphocytes Synaptophysin Hippocampus Mice Transgenic Beta-amyloid Immune tolerance lcsh:RC321-571 Mice Immune system Cognition Alzheimer Disease mental disorders medicine Animals Humans Cognitive decline lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Amyloid beta-Peptides Microglia business.industry Immunotherapy Alzheimer's disease Adoptive Transfer nervous system diseases Disease Models Animal medicine.anatomical_structure Cognitive impairment Neurology Lymphocyte Transfusion Immunology Synapses business |
| Zdroj: | Neurobiology of Disease, Vol 23, Iss 2, Pp 351-361 (2006) |
| ISSN: | 0969-9961 |
| Popis: | Active and passive Abeta immunotherapy provide behavioral benefits in AD transgenic mice, but they can also induce adverse immune over-activation and neuropathological effects. Here, we show that a restricted Abeta-specific immune re-activation can provide cognitive and pathological benefits to APPsw + PS1 transgenic mice for at least 2 1/2 months. A single infusion of Abeta-specific immune cells from Abeta-vaccinated littermates improved performance in cognitively impaired APP + PS1 mice. Recipients had lower levels of soluble Abeta in the hippocampus, less plaque-associated microglia, and more intense synaptophysin immunoreactivity, compared with untreated controls. However, Abeta-specific infusates enriched for Th1 or depleted of CD4(+) T-cells were not effective, nor were ovalbumin-specific infusates. These benefits occurred without global or brain-specific inflammatory responses. Chronically high levels of Abeta can cause immune tolerance, hypo-responsiveness, or anergy to Abeta, but our findings demonstrate that Abeta-specific immune cells can resume endogenous Abeta-lowering processes and may be an effective Abeta therapeutic. |
| Databáze: | OpenAIRE |
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