Mouse models of Anti-Aβ immunotherapies

Abstract

Background: The development of anti-amyloid-beta (Aβ) immunotherapies as the first disease modifying therapy for Alzheimer's Disease (AD) is a breakthrough of basic research and translational science.

Main text: Genetically modified mouse models developed to study AD neuropathology and physiology were used for the discovery of Aβ immunotherapies and helped ultimately propel therapies to FDA approval. Nonetheless, the combination of modest efficacy and significant rates of an adverse side effect (amyloid related imaging abnormalities, ARIA), has prompted reverse translational research in these same mouse models to better understand the mechanism of the therapies.

Conclusion: This review considers the use of these mouse models in understanding the mechanisms of Aβ clearance, cerebral amyloid angiopathy (CAA), blood brain barrier breakdown, neuroinflammation, and neuronal dysfunction in response to Aβ immunotherapy.

Keywords: ARIA; Alzheimer’s disease; Amyloid-beta; Blood brain barrier; Cerebral amyloid angiopathy; Immunotherapy; Microglia; Mouse models; Neuronal dysfunction.