RESEARCH: ALZHEIMERS
FOLDING PROJECT #18206 PROFILE

Alzheimer's disease is a serious problem with no cures. Some versions of the ApoE gene seem to protect against it, while others increase risk. This project uses computer simulations to understand how different ApoE versions work, hoping to lead to new treatments for Alzheimer's.

Note: This TLDR is a simplication and may not be 100% accurate.

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.

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Alzheimer's disease

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

Alzheimer's disease is a serious brain disorder that causes problems with memory, thinking, and behavior. It slowly damages the brain over time, leading to difficulties with everyday activities. There are currently no cures for Alzheimer's disease, but treatments can help manage symptoms and improve quality of life.

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Genetic polymorphisms

Variations in DNA sequences among individuals.

Genetic polymorphisms are differences in the DNA sequence between people. These variations can affect a person's risk for certain diseases, their response to medications, and other traits. Scientists study genetic polymorphisms to understand how genes influence health and disease.

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Apolipoprotein E (ApoE)

A protein that plays a role in lipid metabolism and transport.

ApoE is a protein that helps move fats (lipids) through the body. It's involved in processes like cholesterol transport and brain health. Different versions of ApoE can affect a person's risk for Alzheimer's disease.

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Alleles

Alternative forms of a gene.

Alleles are different versions of the same gene. For example, a person might inherit one allele for blue eyes from their mother and one allele for brown eyes from their father. The combination of alleles determines a person's traits.

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Amino acid substitution

A change in one amino acid within a protein sequence.

Amino acids are the building blocks of proteins. An amino acid substitution is when one type of amino acid is replaced by another in a protein chain. This can alter the protein's function.

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ApoE2

A variant of Apolipoprotein E.

ApoE2 is a specific version of the ApoE protein. It's associated with a lower risk of developing Alzheimer's disease.

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ApoE4

A variant of Apolipoprotein E.

ApoE4 is a specific version of the ApoE protein. It's associated with an increased risk of developing Alzheimer's disease.

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ApoE3

A variant of Apolipoprotein E.

ApoE3 is a common version of the ApoE protein. It's generally considered to have a neutral effect on Alzheimer's risk.

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ApoE Christchurch

A variant of Apolipoprotein E.

ApoE Christchurch is a rare variant of the ApoE protein that appears to offer some protection against Alzheimer's disease.