%0 Journal Article
%T The central role of T-cell memory in Alzheimer¡¯s disease vaccination
%A Brian Giunta
%A Amanda Ruscin
%A Jon Salemi
%A Alan Wolfson
%J Ageing Research
%D 2010
%I 
%R 10.4081/ar.2010.e5
%X Alzheimer's disease (AD) is the most common progressive neurodegenerative brain disease as well as the most common dementia among the elderly. In the future as the average lifespan continues to extend, the number of AD patients will continue to grow. Amyloid-beta (A¦Â) peptides, in both soluble oligomeric, and insoluble forms, are key in the neuropathogenesis of AD and have thus been a therapeutic target for vaccines. Multiple A¦Â vaccination strategies in animal models of AD have demonstrated a marked reduction in both amyloid burden and neurocognitive deficits. Due to the success of these studies, initial human clinical trials of an active A¦Â vaccine were conducted. These were discontinued due to the development of meningoencephalitis in approximately 6% of the vaccinated AD patients. Studies examining the brains of A¦Â-vaccinated patients developing meningoencephalitis implicate A¦Â-reactive T-cell subsets as major components of this deleterious response to active A¦Â vaccination. To subvert possible meningoencephalitis resulting from A¦Â vaccination second generation of vaccines has been more recently developed. These however have met with little success in humans. To build on these findings, an understanding of the role of T-cells in vaccination against A¦Â is presented in this review. Various methods of A¦Â immunotherapy are reviewed including studies in both animal models and humans. Recent works suggest that A¦Â-derived peptides delivered intranasally or transcutaneously results in effective clearance of A¦Â plaques and improvement of cognitive function in animal models of AD. Moreover, undesired T-cell reactivity appeared to be considerably reduced compared with other active immunization strategies. In spite of the past clinical studies, these findings imply that A¦Â vaccination may be both efficacious and safe depending route of delivery, adjuvant choice, and A¦Â epitope administered.
%U http://www.pagepress.org/journals/index.php/ar/article/view/1441