Authors of this comprehensive analysis discuss the amyloid cascade hypothesis in Alzheimer’s disease (AD), which posits that the accumulation of amyloid-β (Aβ) is a key early event leading to neurodegeneration. Evidence supporting the amyloid hypothesis includes the neurotoxic effects of various amyloid species and the high risk of cognitive decline in individuals with significant brain Aβ burden. The neurotoxicity of these amyloid species has been extensively demonstrated, including their role in instigating tau pathology, synaptic deterioration, and various cellular stresses.

AD research has led to the development of both active and passive anti-amyloid immunotherapies. Active immunotherapy uses immunogens to stimulate an immune response against Aβ, while passive immunotherapy involves the infusion of monoclonal anti-Aβ antibodies. The FDA’s approval of aducanumab and lecanemab, which target plaque Aβ, marks significant progress in AD treatment. However, the journey toward effective AD therapies continues, with ongoing research into better antibodies, innovative trial designs, and an increased focus on diversity and inclusion in clinical research.

Reference: Yadollahikhales G, Rojas JC. Anti-Amyloid Immunotherapies for Alzheimer’s Disease: A 2023 Clinical Update. Neurotherapeutics. 2023;20(4):914-931. doi: 10.1007/s13311-023-01405-0.