The article critically examines the amyloid cascade hypothesis and the efficacy of anti-amyloid monoclonal antibodies in treating Alzheimer's disease (AD). Despite the hypothesis's long-standing presence in the scientific literature, it remains unproven, and the effectiveness of anti-amyloid immunotherapy is questionable. Two antibodies, aducanumab and lecanemab, have been approved by the U.S. Food and Drug Administration (FDA), while a third, donanemab, is under review. The main arguments for these approvals include the presumed removal of cerebral amyloid deposits and a statistical delay in cognitive decline. However, the clinical efficacy of these treatments is less than that of conventional treatments, and the selection of amyloid-positive trial patients using non-specific amyloid-PET imaging raises concerns. The article highlights the lack of specificity of amyloid-PET tracers, which can also target inflammation and myelin, leading to false positives. Additionally, the reported amyloid removal during treatment may be influenced by therapy-related brain damage, causing significant adverse effects. The authors call for a more thorough investigation of the negative impact of passive immunotherapy on the brain and suggest shifting the focus to new and more promising diagnostic and therapeutic options, such as infection and hypoperfusion due to cerebral microcalcifications. They recommend that the FDA and CMS ensure proper documentation and neuropathological examination of patients who die during passive immunotherapy trials.The article critically examines the amyloid cascade hypothesis and the efficacy of anti-amyloid monoclonal antibodies in treating Alzheimer's disease (AD). Despite the hypothesis's long-standing presence in the scientific literature, it remains unproven, and the effectiveness of anti-amyloid immunotherapy is questionable. Two antibodies, aducanumab and lecanemab, have been approved by the U.S. Food and Drug Administration (FDA), while a third, donanemab, is under review. The main arguments for these approvals include the presumed removal of cerebral amyloid deposits and a statistical delay in cognitive decline. However, the clinical efficacy of these treatments is less than that of conventional treatments, and the selection of amyloid-positive trial patients using non-specific amyloid-PET imaging raises concerns. The article highlights the lack of specificity of amyloid-PET tracers, which can also target inflammation and myelin, leading to false positives. Additionally, the reported amyloid removal during treatment may be influenced by therapy-related brain damage, causing significant adverse effects. The authors call for a more thorough investigation of the negative impact of passive immunotherapy on the brain and suggest shifting the focus to new and more promising diagnostic and therapeutic options, such as infection and hypoperfusion due to cerebral microcalcifications. They recommend that the FDA and CMS ensure proper documentation and neuropathological examination of patients who die during passive immunotherapy trials.