Recent Advances in Alzheimer’s Disease Treatments with Therapeutic Antibodies to Amyloid-β

Abstract

Alzheimer's disease (AD) is one of the most prevalent and devastating neurodegenerative disorders which affects tens of millions of patients. It imposes significant physical, emotional, and financial burdens on patients, families, and society. Formation of Amyloid-β (Aβ) plaques from the accumulation of Aβ peptides in the cortex and hippocampal region is considered one of the fundamental neuropathological pillars of the disease. Pathological Aβ peptides are generated from its precursor protein through proteolysis. Four small molecule medications were approved by the U. S. Food and Drug Administration (FDA) since 1968 to treat the cognitive symptoms of AD, but they are not curative and have no effect on the development of AD. At least four anti-Aβ antibodies and dozens of other anti-Aβ small molecule agents have been evaluated in clinical trials in the past decades but none of them showed consistent clinical efficacy, presumably because they cannot remove Aβ plaques effectively enough or other reasons such as the patient selection and trial design. Despite the failures, more anti-Aβ antibodies are under development, aiming for more efficient Aβ plaques removal through selectively targeting Aβ oligomers. Among those aducanumab was approved by FDA in 2021 as the first drug to address the underlying biology of AD rather than the symptoms.