Amyloid-beta (Aβ) aggregates (Aβ aggregates)

Aggregated amyloid-beta (Aβ) plaques and fibrils are extracellular protein deposits primarily composed of Aβ42 peptides, which result from the proteolytic cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases (NIH, 2023). These aggregates are a hallmark pathological feature of Alzheimer's disease and are thought to drive neurodegeneration by inducing synaptic loss, oxidative stress, and neuroinflammation (StatPearls, 2024). Therapeutic strategies targeting these aggregates involve monoclonal antibodies designed to recognize specific conformational epitopes unique to the aggregated state, such as protofibrils or insoluble plaques (Nature Medicine, 2023). By binding to these targets, the drugs promote the clearance of existing plaques through microglial activation and inhibit the formation of new toxic species. Clinical success with agents like lecanemab and donanemab has validated Aβ aggregates as a viable therapeutic target for slowing cognitive decline in early-stage Alzheimer's patients (NEJM, 2023). However, treatment is often complicated by safety concerns such as Amyloid-Related Imaging Abnormalities (ARIA), which require careful monitoring via MRI (FDA, 2023).

Other names

Amyloid-beta plaquesAβ fibrilsSenile plaquesNeuritic plaquesAmyloid-beta 42 aggregatesAβ protofibrilsInsoluble amyloid-beta deposits

Monoclonal antibodies bind to specific epitopes on aggregated forms of amyloid-beta (fibrils, protofibrils, or plaques), facilitating their clearance via microglial-mediated phagocytosis and preventing further deposition of the peptide into neurotoxic structures (Nature Medicine, 2023; NEJM, 2023).