Amyloid-beta peptide aggregate (Aβ) (Aβ)

Amyloid-beta (Aβ) peptide aggregates, specifically in the form of insoluble fibrils and extracellular plaques, are a primary pathological hallmark of Alzheimer's disease (Selkoe & Hardy, 2016). These aggregates are formed by the proteolytic cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases, leading to the accumulation of Aβ42 and Aβ40 isoforms (NIH, 2023). According to the amyloid cascade hypothesis, the accumulation and deposition of these aggregates trigger a sequence of events including neuroinflammation, tau protein hyperphosphorylation, and synaptic dysfunction (Hardy & Higgins, 1992). This cascade ultimately results in progressive neuronal death and cognitive decline. Therapeutic strategies targeting Aβ aggregates primarily involve monoclonal antibodies designed to recognize specific epitopes on the fibrils or plaques (van Dyck et al., 2023). These agents, such as lecanemab and donanemab, aim to reduce the plaque burden in the brain by stimulating microglial-mediated phagocytosis (Sims et al., 2023). Clinical validation of this target has been achieved through trials showing that plaque clearance correlates with a slowing of clinical decline in early-stage patients (FDA, 2023). However, treatment is associated with amyloid-related imaging abnormalities (ARIA), requiring careful monitoring via MRI (Sperling et al., 2011).

Other names

Amyloid-beta plaqueSenile plaqueNeuritic plaqueAβ fibrilAggregated amyloid-betaAmyloid-beta 42 aggregate

Monoclonal antibodies bind to specific epitopes on aggregated amyloid-beta (fibrils and plaques) to induce Fc-receptor mediated phagocytosis by microglia and direct dissolution of aggregates.