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

Background: High-profile Phase 3 clinical trials of bapineuzumab and solanezumab, antibodies targeted at amyloid-beta (A beta) 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. Discussion: These therapies are based on the assumption that A beta accumulation is the primary pathogenic trigger of AD. Current evidence suggests that A beta 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. Summary: At this juncture it is no longer unreasonable to suggest that further iterations of anti-A beta therapies should be halted. Clinicians and researchers should instead direct their attention toward greater understanding of the biological function of A beta both in healthy and demented brains, as well as the involvement of long-term chronic exposure to stress in the etiology of AD.