Moving beyond anti-amyloid therapy for the prevention and treatment of Alzheimer’s diseaseReport as inadecuate

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BMC Neurology

, 14:169



BackgroundHigh-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.

DiscussionThese 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.

SummaryAt 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.

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

FADFamilial AD

AβAmyloid beta

NCNormal cognition

NC-AβNormal cognition with Aβ

NDF-ADNeurodegeneration-first AD

AF-ADAβ-first AD

Electronic supplementary materialThe online version of this article doi:10.1186-s12883-014-0169-0 contains supplementary material, which is available to authorized users.

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Author: Michael A Castello - John David Jeppson - Salvador Soriano



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