Research: ALZHEIMERS Folding Project #18213

Alzheimer's disease is a significant cause of death in the USA and there are no effective treatments to halt or reverse disease progression.

Genetic polymorphisms (changes to the amino acids that comprise the protein) in apolipoprotein E (ApoE) are one of the strongest predictors of Alzheimer’s disease.

There are three dominant alleles (versions) of ApoE that are found in humans.

Each ApoE allele differs only by a single amino acid substitution.

ApoE3 is most common and carries a neutral risk for AD.

Carriers of ApoE2 (R158C) appear protected from Alzehimer's disease, whereas ApoE4 (C112R) carriers are 12-fold more likely to develop Alzheimer's disease.

How these mutations in ApoE contribute to Alzheimer's disease, as well as how mutations in ApoE impact ApoE function, remains unclear. It is clear that ApoE isoforms can protect from Alzheimer's, suggesting that ApoE targeted therapeutics may be a means of reversing or preventing Alzheimer's disease progression. In other p182XX projects we have simulated ApoE variants to try to understand the conformations that ApoE adopts in solution.

We are also working to verify these findings in the laboratory.

To do this, we must introduce some additional mutations to ApoE to enable it's study.

To ensure our experimental and simulation results agree, we are also simulating ApoE with the mutations required to perform our experiments. As a whole, we hope the simulations of p182XX lead to a better understanding of how ApoE contributes to Alzheimer's disease.