Amyloid-beta (Aβ) plaque (Aβ plaque)

Amyloid-beta (Aβ) plaques are extracellular deposits of misfolded Aβ peptides, primarily the 42-amino acid isoform (Aβ42), which accumulate in the brain parenchyma of patients with Alzheimer's disease [1, 2]. These plaques are a defining pathological hallmark of the disease and are central to the amyloid cascade hypothesis, which posits that Aβ aggregation is the primary driver of neurodegeneration [4, 8]. The formation of these aggregates begins with the proteolytic cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases [12]. The resulting plaques consist of insoluble fibrils that disrupt neuronal communication and trigger secondary processes such as neuroinflammation, oxidative stress, and the formation of intracellular tau tangles [9, 10]. Beyond Alzheimer's, Aβ aggregates also deposit in the walls of cerebral blood vessels, leading to cerebral amyloid angiopathy (CAA) [13]. Therapeutic interventions, particularly monoclonal antibodies like lecanemab and donanemab, are designed to target these aggregated forms to promote their clearance by microglia [3, 6]. Monitoring of target engagement and treatment efficacy is typically performed using amyloid PET imaging or fluid-based biomarkers [6, 14]. While these therapies have demonstrated the ability to significantly reduce plaque burden in clinical trials, their overall impact on slowing cognitive decline continues to be evaluated [11, 15].

Other names

Senile plaqueNeuritic plaqueAmyloid-beta fibrilAβ aggregateAmyloid plaqueAmyloid-beta peptide aggregate

Monoclonal antibodies bind to aggregated forms of amyloid-beta (fibrils or plaques) and facilitate their clearance via microglial phagocytosis or direct dissolution of the aggregates [3, 6, 7].