Amyloid-beta protein aggregate (Aβ)

Amyloid-beta (Aβ) fibrils and aggregates are insoluble protein assemblies derived from the amyloid precursor protein (APP) through sequential proteolytic cleavage (NIH, 2023). These aggregates, which include soluble oligomers, protofibrils, and insoluble senile plaques, are a primary pathological hallmark of Alzheimer's disease and are central to the amyloid cascade hypothesis (Hardy & Higgins, 1992). They contribute to neurodegeneration by disrupting synaptic function, triggering neuroinflammation, and promoting the spread of tau pathology (PubMed, 2021). In drug development, Aβ aggregates are targeted by monoclonal antibodies designed to selectively bind these misfolded forms rather than monomeric Aβ. By binding to these targets, therapies like lecanemab and donanemab facilitate the clearance of plaques via microglial phagocytosis (Nature Medicine, 2022). Reducing the brain's amyloid burden has been shown to slow cognitive and functional decline in patients with early-stage Alzheimer's disease (NEJM, 2023).

Other names

Amyloid-beta fibrilsBeta-amyloid plaquesAβ aggregatesSenile plaquesAmyloid-beta protofibrilsAmyloid-beta (Aβ) fibrils/aggregates

Monoclonal antibodies target specific epitopes on amyloid-beta aggregates, such as protofibrils or insoluble plaques, to facilitate their clearance from the brain. This is primarily achieved through Fc-receptor-mediated phagocytosis by microglial cells (Nature Reviews Drug Discovery, 2023). Additionally, some agents may prevent the further polymerization of soluble monomers into toxic fibrillar species or promote the dissolution of existing aggregates (Science, 2021).