Clinical trials in Alzheimer's disease': immunotherapy approaches

Recent advances in the understanding of Alzheimers disease pathogenesis have led to the development of numerous compounds that might modify the disease process. Amyloid beta (A beta) peptide represents an important molecular target for intervention in Alzheimers disease. Several types of A beta peptide immunotherapy for Alzheimers disease are under investigation, direct immunization with synthetic intact A beta 42, active immunization involving the administration of synthetic fragments of A beta peptide conjugated to a carrier protein and passive administration with monoclonal antibodies directed against A beta peptide. Pre-clinical studies showed that immunization against A beta peptide can provide protection and reversal of the pathology of Alzheimers disease in animal models. Indeed, several adverse events have been described like meningoencephalitis with AN1792, vasogenic edema and microhemorrhages with bapineuzumab. Although immunotherapy approaches resulted in clearance of amyloid plaques in patients with Alzheimers disease, this clearance did not show significant cognitive effect for the moment. Currently, several A beta peptide immunotherapy approaches are under investigation but also against tau pathology.