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Accumulating data have suggested that controlled cross talk between the peripheral immune system and the resident immune cells is pivotal for arresting neurodegenerative conditions. We have previously discovered that repeated vaccinations of AD transgenic mice with glatiramer acetate (GA), increased recruitment of myeloid-derived cells to the brain that led to a significant decrease in Alzheimer's disease (AD)-like neuropathology, as well as improved cognition and hippocampal neurogenesis. Here, we tested the local effect of boosting a peripheral immune response in AD transgenic mouse brains, achieved by repeated injections of bone marrow-derived dendritic cells (DCs) pulsed in vitro with myelin-derived peptide. We have demonstrated that DC-based vaccination led to a substantial attenuation of AD-like pathology, including diminished Aβ-plaque burden and soluble Aβ(1-42) peptides, reduced astrogliosis and scar tissue protein (CSPG), as well as enhanced astrocyte-related glutamate buffering mechanism (GLT-1). We attribute this benefit observed in the brains of DC-vaccinated AD transgenic mice to the phenotypic shift of microglia/macrophages, manifested by significant reduction of pro-inflammatory (TNFα) and increase of the anti-inflammatory (IL-10) cytokines. Along with extensive elevation in IL-10, this immune-based therapy led to substantial increase in levels of growth factors (IGF-1 and TGFβ) in the brain. Taken together, our results suggest that immunomodulation following DC-based vaccination represents a new disease-modifying therapy for Alzheimer's disease.
Koronyo‐Hamaoui et al. (Thu,) studied this question.