Amyloid-beta precursor protein (APP) processing and amyloid beta peptide production (Aβ production)

Amyloid beta peptide production is the process by which amyloid-beta peptides (typically 36–43 amino acids in length) are formed from amyloid-beta precursor protein (APP) via sequential proteolytic cleavage by beta-secretase (BACE1) and gamma-secretase[1][3][5][6][7]. These peptides are normally released from neurons and oligodendrocytes, but abnormal accumulation and aggregation into soluble oligomers and fibrillar plaques in the brain are a hallmark of Alzheimer's disease pathogenesis[1][3][8][9]. Aβ can interact with cell surface receptors, lipoproteins, and metals, potentially influencing cell signaling, oxidative stress response, and antimicrobial activity, although its physiological function is incompletely understood[1][7][9]. Therapeutic strategies focus on reducing Aβ production, aggregation, or enhancing its clearance, with antibody-based drugs (Aducanumab, Donanemab, Lecanemab) showing clinical promise despite safety challenges such as ARIA[2][4][5][8]. Aβ production, aggregation, and clearance remain central therapeutic targets in Alzheimer’s disease research.

Other names

Amyloid beta peptide productionAmyloid-beta generationAmyloidogenic processingAβ biogenesisBeta-amyloid peptide generationAPP processing (amyloidogenic pathway)

Direct binding to Aβ (neutralizing antibodies—Aducanumab, Donanemab, Lecanemab); Inhibition of β- or γ-secretase to reduce Aβ generation; Enhancement of Aβ clearance (immunotherapy, upregulation of proteases); Disruption of Aβ aggregation (peptidic inhibitors, chelators)