Molecular Mechanisms of the R61T Mutation in Apolipoprotein E4: A Dynamic Rescue (Biophysical Journal)

The apolipoprotein E4 (ApoE4) gene is the strongest genetic risk factor for Alzheimer`s disease (AD). With respect to the other common isoforms of this protein (ApoE2 and ApoE3), ApoE4 is characterized by lower stability that underlies the formation of a stable interaction between the protein`s N- and C-terminal domains. AD-related cellular dysfunctions have been linked to this ApoE4 misfolded state. In this regard, it has been reported that the mutation R61T is able to rescue the deleterious cellular effects of ApoE4 by preventing the formation of the misfolded intermediate state.