Vaccination Strategies for Alzheimer???s Disease

Abstract

The pathological hallmarks of Alzheimer's disease (AD) include beta-amyloid (Abeta) plaques, dystrophic neurites and neurofibrillary pathology, which eventually result in the degeneration of neurons and subsequent dementia. In 1999, international interest in a new therapeutic approach to the treatment of AD was ignited following transgenic mouse studies that indicated that it might be possible to immunise against the pathological alterations in Abeta that lead to aggregation of this protein in the brain. A subsequent phase I human trial for safety, tolerability and immunogenicity using an active immunisation strategy against Abeta had a positive outcome. However, phase IIA human trials involving active immunisation were halted following the diagnosis of aseptic meningoencephalitis in 6% of immunised subjects. Research into immunisation strategies involving transgenic AD mouse models has subsequently been refocused to determine the mechanisms by which plaque clearance and reduced memory deficits are attained, and to establish safer therapeutic approaches that may reduce potentially harmful brain inflammation. The vigour of international research on immunotherapy for AD provides significant hope for a strong therapeutic lead for the escalating number of individuals who will develop this otherwise incurable condition.