Causal treatment of Alzheimer's disease: amyloid antibodies

Abstract

Alzheimer's disease (AD) is the most common cause of dementia. The number of people affected will increase dramatically in the coming decades due to the demographic change. Causal pharmacological approaches have not been available to date. The monoclonal anti-amyloid beta antibody aducanumab was recently approved for the treatment of AD in the USA but was rejected in Europe in December 2021 by the European Medicines Agency (EMA). This review presents the background and rationale for amyloid beta-directed treatment approaches in AD. The focus is on passive immunization with monoclonal anti-amyloid beta antibodies. There are four monoclonal anti-amyloid beta antibodies in an advanced stage of clinical development. Evidence of aclear and significant reduction of the cerebral amyloid load was found for all of them. In the case of aducanumab this has already led to approval by the U.S. Food and Drug Administration (FDA). In the USA donanemab, gantenerumab and lecanemab have received the status of aso-called breakthrough therapy and are expected to go through an accelerated approval process by the FDA in the next 1-2years. Anti-amyloid antibodies represent the first cause-based, disease-modifying therapy for AD approved in the USA. Compared to the near-complete removal of cerebral amyloid plaques, the magnitude of the clinical effect is smaller and the benefit for patients is currently subject to controversial discussions. Nonetheless, the new treatment option represents an important step in the development of effective treatment. Future strategies for the treatment of AD will likely aim at amultimodal concept with different molecular targets. Aprerequisite for all effective disease-modifying therapies will be an early biomarker-based diagnosis prior to the onset of adementia-type syndrome.