Amyloid-beta protein (Aβ) (Aβ)

Amyloid-beta protein aggregates, commonly referred to as plaques, are a primary pathological hallmark of Alzheimer's disease and cerebral amyloid angiopathy [1, 7]. These extracellular deposits are composed of Amyloid-beta (Aβ) peptides, primarily the 40 and 42 amino acid isoforms, which are generated through the sequential proteolytic cleavage of the amyloid precursor protein (APP) by beta-secretase (BACE1) and gamma-secretase enzymes [1, 10]. According to the amyloid cascade hypothesis, the accumulation and aggregation of these proteins into toxic oligomers and insoluble fibrils are central events that drive neurodegeneration, synaptic dysfunction, and neuroinflammation [2, 10]. As a therapeutic target, amyloid-beta plaques have been the focus of extensive pharmaceutical development, specifically for monoclonal antibodies like lecanemab and donanemab that are designed to clear existing deposits and slow cognitive decline in patients with early-stage Alzheimer's disease [5, 19]. The term 'Plaque' is considered an incomplete target name as it refers to a complex pathological structure or lesion rather than a single molecular entity; however, in a clinical and pharmacological context, it almost exclusively refers to these amyloid-beta accumulations in the brain [1, 10, 19].

Other names

Amyloid-beta plaqueA-betaBeta-amyloidSenile plaqueNeuritic plaqueAmyloid depositAbetaAmyloid-beta peptide

Monoclonal antibodies target and bind to aggregated forms of amyloid-beta protein, such as soluble protofibrils and insoluble fibrils found in extracellular plaques. This binding facilitates the clearance of these aggregates from the brain parenchyma through Fc-receptor mediated phagocytosis by microglial cells. Other therapeutic approaches include the use of secretase inhibitors to reduce the production of amyloid-beta monomers or small molecules that prevent the initial aggregation of monomers into toxic oligomers.