Amyloid-β plaque (Aβ plaque)

Amyloid-β plaque refers to the extracellular deposits of aggregated amyloid-β peptides occurring in brain tissue, most notably in the context of Alzheimer’s disease and other neurodegenerative disorders[1][4][5][6][7]. The main constituent of these plaques is the amyloid-β peptide (Aβ), a proteolytic fragment derived from amyloid precursor protein (APP) via sequential cleavage by β-secretase and γ-secretase enzymes[1][7]. Amyloid-β exists in several isoforms, most commonly Aβ40 and Aβ42, with Aβ42 being particularly prone to aggregation and more neurotoxic[1][4]. The aggregation pathway leads from soluble Aβ monomers to oligomers, protofibrils, fibrils, and ultimately insoluble amyloid plaques[1][4][5][6]. Structurally, amyloid-β fibrils assembled in plaques organize into characteristic cross-β-sheet conformations[5][7]. While Amyloid-β plaque accumulation is a histopathological hallmark of Alzheimer’s disease and is targeted by several disease-modifying immunotherapies, mounting evidence shows that plaques themselves may not directly mediate neurotoxicity; rather, intermediate Aβ species, such as oligomers, appear more deleterious to synapses and neurons[5][7]. Amyloid plaques serve as important diagnostic and prognostic biomarkers, especially through PET imaging modalities and fluid biomarker ratios, but challenges surrounding successful clearance include risks of brain edema, ARIA, and uncertain clinical benefit, underlining ongoing controversies in therapeutic targeting[5][7].

Other names

Amyloid plaqueAmyloid-beta plaqueAβ plaqueNeuritic plaqueSenile plaque

Antibody-mediated clearance, Inhibition of aggregation, Enhanced phagocytosis by microglia