Amyloid-beta peptide aggregates (Aβ) (Aβ)

Amyloid-beta (Aβ) peptide aggregates are the hallmark pathological features of Alzheimer's disease, consisting of misfolded peptides derived from the amyloid precursor protein (APP) (PubMed: 31907461). These aggregates exist in various forms, including soluble oligomers, protofibrils, and insoluble fibrils that deposit as extracellular plaques in the brain parenchyma (PubMed: 28913148). The accumulation of these aggregates is thought to trigger a cascade of neurotoxic events, including synaptic loss, tau protein hyperphosphorylation, and chronic neuroinflammation, which collectively lead to cognitive decline (PubMed: 31907461). Therapeutic interventions targeting Aβ aggregates, such as the monoclonal antibodies aducanumab, lecanemab, and donanemab, aim to reduce the plaque burden by facilitating microglial-mediated clearance or neutralizing toxic soluble species (PubMed: 37405448). Clinical trials have demonstrated that reducing Aβ aggregate levels can modestly slow the progression of cognitive impairment in patients with early-stage Alzheimer's disease (PubMed: 36630972). Despite their therapeutic potential, these agents are associated with Amyloid-Related Imaging Abnormalities (ARIA), characterized by brain edema or microhemorrhages, necessitating rigorous safety monitoring (PubMed: 35107464).

Other names

Aβ aggregatesBeta-amyloid plaquesAmyloid-beta fibrilsAmyloid-beta oligomersAbetaSenile plaques

Passive immunotherapy using monoclonal antibodies that bind to specific Aβ species (oligomers, protofibrils, or plaques) to stimulate microglial phagocytosis, promote plaque dissolution, or sequester toxic soluble aggregates (PubMed: 37405448, PubMed: 36630972).