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

作者：Castello Michael A; Jeppson John David; Soriano Salvador^*

来源：BMC Neurology, 2014, 14(1): 169.

DOI：10.1186/s12883-014-0169-0

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

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.

• 出版日期2014-9-2