Abstract: Deposition of aggregated amyloid-β (Aβ) protein in the form of amyloid plaques is a pathological hallmark of Alzheimer’s disease. According to the amyloid hypothesis, Aβ aggregation initiates a pathogenic cascade, eventually leading to dementia. Being the prevailing theory for Alzheimer’s disease, amyloid hypothesis has been used to guide basic research and therapeutic interventions. Supersaturation is a phenomenon that occurs when the concentration of a solute in the solution exceeds its thermodynamic solubility. In the brain, Aβ proteins are usually supersaturated. Aβ aggregation follows the principle of supersaturation (So et al., 2016). In this perspective, I discuss the biochemical implications of Aβ supersaturation in the framework of amyloid hypothesis and how this knowledge can be used to improve therapeutic development for Alzheimer’s disease.