Potential neurotoxic inflammatory responses to Aβ vaccination in humans

Summary.

Studies in transgenic mouse models of Alzheimer's disease suggested the development of a vaccine that would induce the production of antibodies against amyloid-β (Aβ) peptide, which in turn would stimulate microglia to phagocytose and remove senile plaques. However, some patients in the human clinical trials developed symptoms of brain inflammation, demonstrated by lymphocyte infiltration and elevated protein levels. These parameters are indicative of a breakdown of the blood-brain-barrier and entry of T-cells into the brain. Aβ-specific activated T-helper cells have the potential to amplify the existing pro-inflammatory conditions that are present in the brains of Alzheimer's disease patients. Cytotoxic T-cells might even attack the amyloid precursor protein which is present on the surface of many cells, including neurons. Before undertaking further vaccination trials there is a need to re-assess the risks associated with Aβ vaccination and with the therapeutic containment of a neuroinflammatory response. These risks may not be justified in the light of recent studies which have shown the efficacy of conventional, low-risk treatments in slowing the progress of AD.