RESEARCH: ALZHEIMERS
FOLDING PROJECT #18212 PROFILE

Alzheimer's disease is a serious problem with no cure. Different versions of the ApoE gene affect your risk of getting Alzheimer's. Some versions protect against it, while others increase your risk. This project uses computer simulations to study how these different ApoE versions work, hoping to find new ways to treat or prevent Alzheimer's.

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 disease.

Alzheimer's disease is a serious brain disorder that slowly destroys memory and thinking skills. It's the most common cause of dementia, affecting millions worldwide.

Genetic polymorphisms

Variations in DNA sequences among individuals.

Genetic polymorphisms are differences in the DNA sequence between people. These variations can affect how genes function and may contribute to disease risk.

Apolipoprotein E (ApoE)

A protein that transports cholesterol and other lipids in the blood.

ApoE is a crucial protein involved in transporting fats (lipids) throughout the body. It plays a role in brain health and is linked to Alzheimer's disease risk.

Alleles

Different versions of a gene.

Alleles are alternative forms of a gene that determine specific traits. For example, one allele might code for brown eyes while another codes for blue eyes.

Amino acids

The building blocks of proteins.

Amino acids are the fundamental units that make up proteins. There are 20 different amino acids, each with unique properties, that combine in specific sequences to create the diverse functions of proteins.

ApoE4

A variant of the Apolipoprotein E gene associated with increased risk of Alzheimer's disease.

ApoE4 is a specific form of the ApoE gene that significantly raises the likelihood of developing Alzheimer's disease.

ApoE2

A variant of the Apolipoprotein E gene associated with reduced risk of Alzheimer's disease.

ApoE2 is a specific form of the ApoE gene that appears to protect against Alzheimer's disease.

ApoE3

A common variant of the Apolipoprotein E gene with neutral risk for Alzheimer's disease.

ApoE3 is the most prevalent form of the ApoE gene and doesn't significantly increase or decrease the risk of developing Alzheimer's disease.

ApoE Christchurch

A recently discovered variant of the Apolipoprotein E gene associated with reduced risk of Alzheimer's disease.

ApoE Christchurch is a newer variant of the ApoE gene that has shown potential protective effects against Alzheimer's disease.