The
amyloid cascade hypothesis for
Alzheimer's disease is still alive, although heavily challenged. Effective anti-
amyloid immunotherapy would confirm the hypothesis' claim that the
protein amyloid-beta is the cause of the disease. Two
antibodies,
aducanumab and
lecanemab, have been approved by the U.S. Food and Drug Administration, while a third,
donanemab, is under review. The main argument for the FDA approvals is a presumed
therapy-induced removal of cerebral
amyloid deposits.
Lecanemab and
donanemab are also thought to cause some statistical delay in the determination of
cognitive decline. However, clinical efficacy that is less than with conventional treatment, selection of
amyloid-positive trial patients with non-specific
amyloid-PET imaging, and uncertain
therapy-induced removal of cerebral amyloids in clinical trials cast doubt on this anti-Alzheimer's antibody
therapy and hence on the
amyloid hypothesis, calling for a more thorough investigation of the negative impact of this type of
therapy on the brain.