A2M and early-onset autosomal dominant Alzheimer disease: For example, apolipoprotein E (ApoE) is an endogenous ligand of α2M in blood plasma, and the binding of α2M to the ε4 isoform (the strongest known genetic risk factor for Alzheimer's disease) is much less compared to the binding of α2M to the ε2 and ε3 ApoE isoforms [15].