Amyloid-beta immunotherapy for Alzheimer's disease.
Alzheimer's disease (AD) is a progressive, degenerative disorder of the brain and the most common form of dementia among the elderly. As the population grows and lifespan is extended, the number of AD patients will continue to rise. Current clinical therapies for AD provide partial symptomatic benefits for some patients; however, none of them modify disease progression. Amyloid-beta (Abeta) peptide, the major component of senile plaques in AD patients, is considered to play a crucial role in the pathogenesis of AD thereby leading to Abeta as a target for treatment. Abeta immunotherapy has been shown to induce a marked reduction in amyloid burden and an improvement in cognitive function in animal models. Although preclinical studies were successful, the initial human clinical trial of an active Abeta vaccine was halted due to the development of meningoencephalitis in approximately 6% of the vaccinated AD patients. Some encouraging outcomes, including signs of cognitive stabilization and apparent plaque clearance, were obtained in subset of patients who generated antibody titers. These promising preliminary data support further efforts to refine Abeta immunotherapy to produce highly effective and safer active and passive vaccines for AD. Furthermore, some new human clinical trials for both active and passive Abeta immunotherapy are underway. In this review, we will provide an update of Abeta immunotherapy in animal models and in human beings, as well as discuss the possible mechanisms underlying Abeta immunotherapy for AD.
Fu
H J
HJ
Center for Neurologic Diseases, Department of Neurology, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Liu
B
B
Frost
J L
JL
Lemere
C A
CA
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D023582:Alzheimer Vaccines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D004195:Disease Models, Animal; D006801:Humans; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D058225:Plaque, Amyloid / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014611:Vaccination / Q000379:methods / Q000639:trends
D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides