Amyloid-β (β-amyloid)

Amyloid-β (Aβ) is a family of peptides of 36–43 amino acids cleaved from the amyloid precursor protein (APP) by β- and γ-secretase; the 42-residue form (Aβ42) is especially prone to misfolding and aggregation into soluble oligomers and insoluble amyloid plaques. Aβ42 plaques are a defining histopathological feature of Alzheimer's disease, detectable by PET imaging or CSF assay years before clinical symptoms. The amyloid cascade hypothesis proposes Aβ accumulation as an upstream initiator of Alzheimer's pathology, but whether plaques themselves are the primary toxic species or an epiphenomenon remains debated — soluble oligomers rather than fibrillar plaques are now widely regarded as the most neurotoxic form. Anti-amyloid monoclonal antibodies lecanemab (FDA approval 2023, EMA approval 2025) and donanemab (FDA approval 2024) have completed phase-3 trials and received regulatory approval, showing modest but statistically significant slowing of cognitive decline with substantial plaque clearance, lending qualified support to the cascade hypothesis.