Immunotherapy for Alzheimer's disease.
Recent studies in murine models of Alzheimer's disease (AD) have found that active immunisation with amyloid-beta peptide (Abeta) or passive immunisation with Abeta antibodies can lessen the severity of Abeta-induced neuritic plaque pathology through the activation of microglia. These antibodies can be detected in the serum and CSF. Whether they slow down or speed up the development and progression of AD has not been determined. Furthermore, the conditions that induce formation of such antibodies are unknown, or how specific they are to AD. However, the evidence suggests at least a potential beneficial role for some features of neuroinflammation in AD. A clinical phase II study of an active immunisation approach with AN1792 was started in 2001, but was recently suspended after some patients developed serious adverse events. These were most likely caused by the activation of the proinflammatory cascade. Immunotherapy approaches represent fascinating ways to test the amyloid hypothesis and may offer genuine opportunities to modify disease progression. This review focuses on immunisation strategies and details of the pathways involved in antibody clearance of Abeta.
Dodel
Richard C
RC
Department of Neurology, Friedrich-Wilhelms-University Bonn, Germany. richard.dodel@ukb.uni-bonn.de <richard.dodel@ukb.uni-bonn.de>
Hampel
Harald
H
Du
Yansheng
Y
D000544:Alzheimer Disease / Q000276:immunology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000276:immunology; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007167:Immunotherapy; D051379:Mice
D016229:Amyloid beta-Peptides