The aggregation of amyloid-β: from condensation, nucleation, and conformation to targeting therapy.

Senile plaques consist of Amyloid-β (Aβ) are the pathological hallmark of Alzheimer's disease (AD), which is the most common type of neurodegenerative disorder. Aβ is a small peptide that consists of 38 to 43 amino acids. It causes harmful effects through abnormal aggregation, like the formation of oligomers and protofibrils. These aggregates can disrupt normal synaptic function and trigger a series of neuroinflammatory and neurodegenerative changes. The aggregation dynamics of Aβ are modulated by multiple factors, such as conformational transitions, the exposure of hydrophobic segments, liquid-liquid phase separation, and post-translational modifications. These factors can promote the formation of diverse aggregates with distinct conformations. This review summarizes the structural characteristics of various Aβ aggregates, along with related regulatory elements, their effects on cellular processes, and therapeutic strategies targeting Aβ and its aggregates. This overview contributes to a better understanding of the complex mechanisms underlying Aβ aggregation and its pathological consequences, as well as the basis for future therapies targeted to Aβ and aggregates.