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Moving beyond anti-amyloid therapy for the prevention and treatment of Alzheimer’s disease

Michael A Castello, John David Jeppson and Salvador Soriano*

Author Affiliations

Department of Anatomy, Loma Linda University School of Medicine, Evans Hall B08, 24785 Stewart Street, Loma Linda 92354, CA, USA

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BMC Neurology 2014, 14:169  doi:10.1186/s12883-014-0169-0

Published: 2 September 2014



High-profile Phase 3 clinical trials of bapineuzumab and solanezumab, antibodies targeted at amyloid-beta (Aβ) removal, have failed to meet their primary endpoints. Neither drug improves clinical outcomes in patients with late onset AD, joining a long list of unsuccessful attempts to treat AD with anti-amyloid therapies.


These therapies are based on the assumption that Aβ accumulation is the primary pathogenic trigger of AD. Current evidence suggests that Aβ may actually accumulate as part of an adaptive response to long-term chronic brain stress stimuli that would make more suitable candidates for therapeutic intervention.


At this juncture it is no longer unreasonable to suggest that further iterations of anti-Aβ therapies should be halted. Clinicians and researchers should instead direct their attention toward greater understanding of the biological function of Aβ both in healthy and demented brains, as well as the involvement of long-term chronic exposure to stress in the etiology of AD.

Late onset Alzheimer’s disease; Amyloid cascade hypothesis; Anti-amyloid therapy; Amyloid beta; Familial Alzheimer’s disease; Solanezumab; Bapineuzumab; Cholesterol metabolism; Dementia; Neurodegeneration