title: Bapineuzumab and solanezumab for Alzheimer's disease: is the 'amyloid cascade hypothesis' still alive?
abstract: BACKGROUND
  The 'amyloid cascade hypothesis' remains the leading hypothesis to explain the pathophysiology of Alzheimer's disease (AD). Immunotherapeutic agents have been developed to remove the neurotoxic amyloid β42 protein and prevent the hypothesized amyloid β42-induced neurotoxicity and neurodegeneration. The most notable of these immunotherapies are bapineuzumab and solanezumab.
  
  
  METHODS
  This article briefly reviews the experimental agents in development for treatment of AD and then discusses the results of bapineuzumab and solanezumab in AD patients, as reported in preclinical studies, clinical trials and press releases.
  
  
  CONCLUSIONS
  Phase III trials showed that bapineuzumab failed to improve cognitive and functional performances in AD patients, and was associated with a high incidence of amyloid-related imaging abnormalities (ARIA). Solanezumab's two Phase III trials in AD patients failed to meet endpoints when analyzed independently. However, analysis of pooled data from both trials showed a significant reduction in cognitive decline in mild AD patients. The improvement was associated with an increase in plasma amyloid-β (Aβ) levels and a low incidence of ARIA in solanezumab-treated patients. The marginal benefits of solanezumab are encouraging to support continued evaluation in future studies, and offer small support in favor of the ongoing viability of the 'amyloid cascade hypothesis' of AD.
authors.affiliation: McLean Hospital, Harvard Medical School, Department of Psychiatry, 115 Mill Street, Belmont, MA 02478, USA.
authors.forename: Haythum O
authors.initials: HO
authors.lastname: Tayeb
authors.forename: Evan D
authors.initials: ED
authors.lastname: Murray
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Price
authors.forename: Frank I
authors.initials: FI
authors.lastname: Tarazi
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000628:therapy*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C550616:solanezumab; C545458:bapineuzumab