Amyloid-beta (Aβ) fibrillar plaque (Aβ plaque)

Amyloid-beta fibrillar plaques are extracellular deposits of misfolded amyloid-beta (Aβ) peptides, primarily the 42-amino acid isoform (Aβ42), which aggregate into insoluble cross-beta sheet structures (NIH, 2023). These plaques are a defining pathological hallmark of Alzheimer's disease and are frequently found in the parenchyma of the cerebral cortex (StatPearls, 2023). The formation of these deposits is associated with neurotoxicity, synaptic loss, and the activation of neuroinflammatory pathways involving microglia and astrocytes (PubMed, 2020). In the context of drug development, these plaques serve as a primary therapeutic target for monoclonal antibodies such as aducanumab, lecanemab, and donanemab, which aim to reduce the amyloid burden in the brain (FDA, 2023). By binding to the fibrillar or protofibrillar forms of Aβ, these therapies facilitate the clearance of plaques through microglial-mediated phagocytosis, which has been shown to correlate with a slowing of cognitive decline in clinical settings (NEJM, 2023). However, the removal of vascular amyloid can lead to safety concerns known as amyloid-related imaging abnormalities (ARIA), manifesting as edema or microhemorrhages (Nature Reviews Neurology, 2022).

Other names

Amyloid-beta plaqueSenile plaqueNeuritic plaqueAβ fibrilAmyloid deposit

Monoclonal antibodies bind to specific epitopes on amyloid-beta fibrils or plaques, facilitating their clearance via microglial phagocytosis (Fc-receptor mediated) or preventing further aggregation of soluble species into insoluble deposits (PubMed, 2021).