Beta amyloid A4 protein aggregate (Aβ aggregate)

Beta amyloid A4 protein aggregate (Aβ aggregate) is a pathological complex formed by the aggregation of amyloid-beta (Aβ) peptides, which are fragments derived from the amyloid precursor protein (APP) through sequential cleavage by β- and γ-secretase enzymes. These Aβ peptides, typically 36-43 amino acids long, are prone to misfold, forming soluble oligomers, protofibrils, and ultimately insoluble amyloid plaques. Aggregates composed of Aβ are central to the molecular pathology of Alzheimer’s disease and cerebral amyloid angiopathy, driving neurotoxicity through synaptic dysfunction, neuroinflammation, and neuronal death. Therefore, these aggregates are key therapeutic targets, with drug development efforts aiming to prevent formation, promote clearance, or neutralize toxicity through immunotherapies and small molecules. Oligomeric and fibrillar Aβ aggregates are monitored by CSF and imaging biomarkers in clinical practice and trials. Safety concerns are substantial, especially risk of ARIA and poor efficacy in some genotypes, which complicate therapeutic targeting.

Other names

Amyloid-beta aggregateAβ aggregateAmyloid-beta plaqueBeta-amyloid plaqueAmyloid plaqueAbeta aggregateBeta amyloid A4 aggregate

Immunotherapy: Antibody-mediated clearance of Aβ aggregates from brain tissue (e.g., Aducanumab, Bapineuzumab); Small molecule inhibition: Prevents aggregation or promotes disaggregation; Inhibition of Aβ production: By targeting upstream processing enzymes (β- and γ-secretase); Promotion of aggregate clearance via activation of microglia