The article discusses the amyloid hypothesis for Alzheimer's disease (AD) and the effectiveness of antibody therapies targeting amyloid-beta (Aβ). While two antibodies, aducanumab and lecanemab, have been approved by the FDA, and a third, donanemab, is under review, their clinical efficacy remains questionable. The main argument for approval is the presumed removal of cerebral amyloid deposits, but clinical trials show only minor delays in cognitive decline, and the results are not significantly better than conventional treatments. The use of amyloid-PET imaging as an entry criterion for trials is also problematic, as it may include patients without AD, and the interpretation of amyloid-PET signals is often non-specific. The article highlights the lack of specificity of amyloid-PET probes, which can bind to inflammation and myelin, leading to false positives. Additionally, the removal of amyloid reported in trials may be due to therapy-induced brain damage rather than actual amyloid clearance. The article also notes the occurrence of adverse events, such as ARIA (Amyloid-Related Imaging Abnormalities), and the lack of long-term follow-up data. The authors argue that the amyloid hypothesis and antibody therapies need further investigation due to their limited efficacy and potential negative impact on the brain. The article calls for a shift in focus away from amyloids and towards more promising diagnostic and therapeutic approaches.The article discusses the amyloid hypothesis for Alzheimer's disease (AD) and the effectiveness of antibody therapies targeting amyloid-beta (Aβ). While two antibodies, aducanumab and lecanemab, have been approved by the FDA, and a third, donanemab, is under review, their clinical efficacy remains questionable. The main argument for approval is the presumed removal of cerebral amyloid deposits, but clinical trials show only minor delays in cognitive decline, and the results are not significantly better than conventional treatments. The use of amyloid-PET imaging as an entry criterion for trials is also problematic, as it may include patients without AD, and the interpretation of amyloid-PET signals is often non-specific. The article highlights the lack of specificity of amyloid-PET probes, which can bind to inflammation and myelin, leading to false positives. Additionally, the removal of amyloid reported in trials may be due to therapy-induced brain damage rather than actual amyloid clearance. The article also notes the occurrence of adverse events, such as ARIA (Amyloid-Related Imaging Abnormalities), and the lack of long-term follow-up data. The authors argue that the amyloid hypothesis and antibody therapies need further investigation due to their limited efficacy and potential negative impact on the brain. The article calls for a shift in focus away from amyloids and towards more promising diagnostic and therapeutic approaches.