PROJECT #18206 RESEARCH FOR ALZHEIMERS
FOLDING PERFORMANCE PROFILE

PROJECT SUMMARY

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. Finally, a recent variant in ApoE3, ApoEchristchurch (R136S) has emerged which also appears to protect from 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. Here, we will simulate how one varaiants of ApoE move in solution. We hope these simulations will lead to a better understanding of how ApoE contributes to Alzheimer's disease.

PROJECT INFO

Manager(s): Justin Miller

Institution: Washington University in St. Louis

PROJECT WORK UNIT SUMMARY

Atoms: 302,700

Core: GRO_A8

Status: Public