The mechanisms and consequences of plaque removal following Abeta immunotherapy in human Alzheimer's disease

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Alzheimer’s disease (AD) is the commonest cause of dementia in old age. In AD a protein known as amyloid-beta (A?) accumulates in the brain regions critical for learning and memory.Recently in animal studies immunization with A? has been shown to result in removal of A? from the brain associated with improvement in brain function. Some preliminary results of the initial human clinical trials suggested a slower cognitive deterioration in patients with an appropriate immune response.The precise mechanism by which the activated immune system removes Ab is as yet unclear. Furthermore, some patients developed cerebral inflammatory complications, halting the clinical trials. Access to post mortem brain tissue from patients participating in the clinical trial of Ab immunotherapy puts us in a unique position to address important questions. We aim to clarify: (i) the mechanism(s) of Ab plaque removal (ii) if plaque removal can take place without the unwanted side effects of severe cerebral inflammation and (iii) the consequences of Ab removal on the other features of AD pathology.This information is important in order to inform the second generation of trials of Ab immunotherapy which are already underway.