ApoER2 splice variants can act as a receptor for alpha-2-macroglobulin which can have a role in clearance of alpha-2-macroglobulin/proteinase complex. Proteases may play a role in synaptic plasticity balancing proteolytic activity and inhibition, which is controlled by proteolytic inhibitors such as alpha-2-macroglobulin. Studies have shown that a high presence of alpha-2-macroglobulin is present in the neuritic plaques in many Alzheimer patients. Isolation of cDNA encoding proteins associated with Aβ was used to discover alpha-2-macroglobulin. These discoveries may link alpha-2-macroglobulin and its receptors, one of them being ApoER2, to Alzheimer's disease.