Amyloid-beta peptide fibrillar aggregate (Aβ plaque)

Fibrillar aggregated amyloid-beta (Aβ) plaques are extracellular deposits of misfolded Aβ peptides, predominantly the 42-amino acid variant (Aβ42), that accumulate in the cortical gray matter of patients with Alzheimer's disease (Selkoe & Hardy, 2016). These aggregates are formed through the proteolytic cleavage of the amyloid precursor protein (APP) and subsequent self-assembly into insoluble beta-sheet structures. The presence of these plaques is a defining neuropathological criterion for Alzheimer's and is closely linked to neuroinflammatory responses and synaptic dysfunction. Therapeutic strategies targeting these plaques involve monoclonal antibodies that selectively bind to the fibrillar or protofibrillar species (Sevigny et al., 2016). By binding to the plaques, these agents recruit microglial cells to clear the deposits through phagocytosis, aiming to slow the progression of cognitive impairment (FDA, 2023; FDA, 2024). However, the removal of vascular amyloid can lead to weakened vessel walls, resulting in safety concerns such as amyloid-related imaging abnormalities (ARIA) (Sperling et al., 2011).

Other names

Amyloid-beta plaquesSenile plaquesNeuritic plaquesFibrillar amyloid-betaAβ fibrilsAmyloid-beta aggregates

Monoclonal antibodies bind to aggregated amyloid-beta species (fibrils and plaques) in the brain, which then triggers microglial-mediated clearance of the protein deposits through Fc-receptor-mediated phagocytosis (Sevigny et al., 2016; FDA, 2023).