RESEARCH: ALZHEIMERS
FOLDING PROJECT #18211 PROFILE

Alzheimer's is a deadly disease with no cure. Changes in the ApoE gene can either protect against or increase the risk of Alzheimer's. This project uses computer simulations to study how different versions of ApoE move, hoping to unlock secrets about how ApoE affects Alzheimer's and lead to new treatments.

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.

Alzheimer's disease

A progressive neurodegenerative disorder characterized by memory loss and cognitive decline.

Alzheimer's disease is a serious brain condition that slowly destroys memory and thinking skills. It is the most common cause of dementia, affecting millions of people worldwide. There is no cure for Alzheimer's, but treatments can help manage symptoms.

Genetic polymorphisms

Variations in DNA sequences among individuals.

Genetic polymorphisms are differences in the DNA sequence between people. These variations can affect how genes work and may contribute to differences in traits and diseases.

Apolipoprotein E (ApoE)

A protein that carries cholesterol in the blood.

ApoE is a protein that plays a crucial role in transporting cholesterol throughout the body. It helps regulate lipid levels and is involved in various biological processes.

Alleles

Different versions of a gene.

Alleles are alternative forms of a gene that occupy the same position (locus) on a chromosome. They can code for different variations of a trait.

Amino acids

The building blocks of proteins.

Amino acids are the fundamental units that make up proteins. They link together in specific sequences to form long chains, creating diverse protein structures with various functions.

ApoE2 (R158C)

A specific variant of the ApoE gene associated with a reduced risk of Alzheimer's disease.

ApoE2 (R158C) is a genetic variant that appears to protect against Alzheimer's disease. Individuals carrying this variant have a lower risk of developing the condition.

ApoE4 (C112R)

A specific variant of the ApoE gene associated with an increased risk of Alzheimer's disease.

ApoE4 (C112R) is a genetic variant that significantly elevates the risk of developing Alzheimer's disease. Individuals carrying this variant are 12 times more likely to develop the condition.

ApoEchristchurch (R136S)

A recent variant of the ApoE gene associated with a reduced risk of Alzheimer's disease.

ApoEchristchurch (R136S) is a recently identified genetic variant that appears to protect against Alzheimer's disease. It carries a similar protective effect as ApoE2.