Amyloid-beta peptide formation (Aβ formation)

Amyloid-beta formation refers to the biological process by which amyloid-beta (Aβ) peptides are generated from the proteolytic cleavage of amyloid precursor protein (APP) by β-secretase and γ-secretase enzymes. These peptides—primarily Aβ40 and Aβ42—can aggregate into soluble oligomers and insoluble fibrils that deposit as plaques in brain tissue. The accumulation of these aggregates is a hallmark of Alzheimer’s disease pathology[1][2][3][4][7]. Aβ monomers can have physiological roles at low concentrations, including modulation of synaptic transmission and neuroprotection. However, when production exceeds clearance capacity or when mutations favor aggregation-prone forms like Aβ42 or Aβ43, toxic oligomers form that disrupt cellular function through oxidative stress, membrane permeabilization, impaired cell signaling, and ultimately neuronal death[1][3][8]. The transition from α-helical to β-sheet structure is critical for fibril assembly; this conformational change is influenced by sequence mutations and environmental factors such as metal ions[1][2]. Therapeutic strategies have targeted various steps in this pathway—including inhibition of secretases to reduce peptide generation or immunotherapies aimed at clearing aggregated forms—but with limited clinical success so far due to both lack of efficacy on cognitive outcomes and safety concerns related to immune-mediated side effects[3]. Important note: "Amyloid-beta formation" describes a *process*, not a discrete molecular target such as an enzyme or receptor. Therefore it does **not** fit standard definitions for therapeutic targets used in drug discovery databases. If you are seeking information about specific molecular targets involved in this pathway—for example "Amyloid precursor protein" (APP), "Beta-secretase 1" (BACE1), "Gamma-secretase", or "Amyloid beta peptide" itself—please specify one of those molecules.

Other names

Amyloid-β aggregationAβ aggregationAmyloid plaque formationβ-amyloid fibrillogenesis