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

Amyloid-beta fibrillar plaques are extracellular deposits of misfolded amyloid-beta (Aβ) peptides, primarily the 42-amino acid isoform (Aβ42), which serve as a defining pathological hallmark of Alzheimer's disease (NIH, 2023). These plaques form through the sequential proteolytic cleavage of the amyloid precursor protein (APP) by beta-secretase (BACE1) and gamma-secretase, resulting in the accumulation of insoluble fibrils characterized by a cross-beta sheet structure (PubChem, 2024). While soluble Aβ oligomers are often considered the most neurotoxic species, the presence of fibrillar plaques is strongly associated with the progression of neurodegeneration and is used as a primary diagnostic criterion (PubMed, 2023). Therapeutic interventions, specifically anti-amyloid monoclonal antibodies like lecanemab and donanemab, are designed to recognize these aggregates and stimulate the immune system to clear them from the brain (FDA, 2023). Clinical trials have demonstrated that significant reduction in plaque burden can lead to a modest slowing of cognitive and functional decline in patients with early-stage Alzheimer's disease (StatPearls, 2024). However, targeting these plaques is associated with specific safety risks, most notably Amyloid-Related Imaging Abnormalities (ARIA), which require careful monitoring via MRI (Alzheimer's Association, 2024).

Other names

Senile plaqueNeuritic plaqueAmyloid plaqueAβ fibrilBeta-amyloid aggregateInsoluble amyloid-beta deposit

Monoclonal antibodies bind to specific conformational epitopes on amyloid-beta fibrils or plaques, facilitating their clearance from the brain parenchyma through microglial-mediated phagocytosis and Fc-receptor-mediated transport across the blood-brain barrier (PubMed, 2023; FDA, 2023).