Amyloid-beta (Aβ) fibrils and plaques (Aβ)

Aggregated amyloid-beta (Aβ) fibrils and plaques are extracellular protein deposits primarily composed of misfolded Aβ peptides, which are cleavage products of the amyloid precursor protein (APP). These aggregates are a hallmark pathological feature of Alzheimer's disease and are thought to play a central role in neurodegeneration by inducing synaptic dysfunction, neuroinflammation, and oxidative stress (NIH, 2023). In a healthy brain, Aβ monomers are typically cleared, but in disease states, they assemble into oligomers, protofibrils, and eventually insoluble fibrils that form plaques (PubMed, PMID: 33098754). Therapeutic strategies targeting these aggregates involve monoclonal antibodies designed to recognize and bind to the fibrillar or protofibrillar forms of the protein. By binding to these targets, the drugs stimulate the immune system, particularly microglia, to engulf and remove the plaques (FDA, 2023). Recent clinical successes with drugs like lecanemab and donanemab have validated Aβ plaque reduction as a surrogate endpoint for slowing cognitive decline in early-stage Alzheimer's patients (NEJM, 2023). However, targeting these aggregates is associated with specific safety risks, most notably Amyloid-Related Imaging Abnormalities (ARIA), which require careful monitoring via MRI. Despite these challenges, the clearance of aggregated Aβ remains a primary focus of drug development for modifying the course of neurodegenerative amyloidopathies.

Other names

Amyloid-beta plaquesSenile plaquesAβ aggregatesAmyloid-beta fibrilsNeuritic plaquesAmyloid-beta protofibrils

Monoclonal antibodies target specific epitopes on Aβ aggregates, facilitating their clearance via microglial-mediated phagocytosis and preventing further deposition (StatPearls, 2023).