Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common causes of dementia and movement disorders in the elderly. While progressive accumulation of oligomeric amyloid-beta protein (Abeta) has been identified as one of the central toxic events in AD leading to synaptic dysfunction, accumulation of alpha-synuclein (alpha-syn) resulting in the formation of oligomers has been linked to PD. Most of the studies in AD have been focused on investigating the role of Abeta and Tau; however, recent studies suggest that alpha-syn might also play a role in the pathogenesis of AD. For example, fragments of alpha-syn can associate with amyloid plaques and Abeta promotes the aggregation of alpha-syn in vivo and worsens the deficits in alpha-syn tg mice. Moreover, alpha-syn has also been shown to accumulate in limbic regions in AD, Down's syndrome, and familial AD cases. Abeta and alpha-syn might directly interact under pathological conditions leading to the formation of toxic oligomers and nanopores that increase intracellular calcium. The interactions between Abeta and alpha-syn might also result in oxidative stress, lysosomal leakage, and mitochondrial dysfunction. Thus, better understanding the steps involved in the process of Abeta and alpha-syn aggregation is important in order to develop intervention strategies that might prevent or reverse the accumulation of toxic proteins in AD.