Amyloid-β peptide aggregation (Aβ aggregation)

Amyloid-β aggregation involves the progressive association of amyloid-β (Aβ) peptides—mainly Aβ40, Aβ42, and Aβ43—into soluble oligomers, protofibrils, and insoluble amyloid fibrils. This process is central to Alzheimer’s disease pathology, where aggregated Aβ forms extracellular plaques and disrupts neuronal function. The aggregation pathway begins with monomeric Aβ, which misfolds and nucleates to form oligomers and then mature fibrils by a sequence of nucleation and elongation steps[1][2][3][6][7]. Aggregated Aβ is neurotoxic, mediates synaptic dysfunction, and induces cell death, contributing to cognitive decline. Numerous drugs—including monoclonal antibodies and small molecules—target Aβ aggregation, aiming to disrupt this process or clear existing aggregates[4][5]. Quantitative biomarkers such as cerebrospinal fluid Aβ levels and imaging of amyloid plaques are used for patient selection and efficacy monitoring[4]. While Aβ aggregation is a validated therapeutic target, challenges exist in drug safety and the full understanding of which Aβ species drive disease progression[4][5].

Other names

Amyloid-beta aggregationAmyloid β aggregationAβ self-associationAmyloid fibril formationβ-amyloid aggregation

Immunotherapy (antibodies bind aggregated Aβ and mediate clearance); Aggregation inhibition (preventing or disrupting Aβ peptide self-assembly/fibril formation); Chelation (modulate metal-Aβ interaction, reduce aggregation); Small molecules and peptides (direct inhibition of nucleation/elaboration steps)