<p>The misfolding and subsequent brain accumulation of two intrinsically disordered proteins, amyloid-beta (Aβ) and tau, are considered major hallmarks of Alzheimer's disease (AD), a neurodegenerative disorder characterized by cognitive decline and memory loss. Aβ accumulates extracellularly in the brain parenchyma, while tau aggregates intracellularly within neurons. Understanding the underlying molecular mechanisms is essential for uncovering the origins of AD and has remained an active area of research for over three decades, with the aim of developing therapeutics to mitigate or prevent disease progression. Our research group has made significant contributions over the years to explore the Aβ aggregation process, with particular emphasis on unraveling the role played by the solvent in guiding the process using large-scale atomistic molecular dynamics simulations. More recently, we have expanded our focus to probe the microscopic mechanism of aggregation of the tau protein. Some of the important findings that originated from our work have been presented in this review.</p> Graphical abstract <p>Alzheimer's disease is caused due to aggregation of two intrinsically disordered proteins (IDP), amyloid-β and tau. Simulation studies have unravelled that water plays a pivotal role in the aggregation process. A schematic image depicting water molecules confined within the core and at the surface of an IDP aggregate is shown.</p>