RESEARCH: ALZHEIMERS
FOLDING PROJECT #18200 PROFILE

Alzheimer's disease is a serious problem with no cure. A gene called ApoE affects your risk of getting it. Some versions of ApoE protect against Alzheimer's, while others increase the risk. This project uses computer simulations to understand how ApoE works and how it might be used to treat 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.

How these mutations in ApoE contribute to Alzheimer's disease, as well as how mutations in ApoE impact ApoE function, remains unclear. However, 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 varaiant of ApoE, ApoE4, moves in solution.

We hope these simulations will lead to a better understanding of how ApoE contributes to Alzheimer's disease.

in future projects, we will simulate the other ApoE isoforms in an effort to understand how they protect from Alzheimer's disease.

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Alzheimer's disease

A progressive neurodegenerative disorder that affects memory, thinking, and behavior.

Alzheimer's disease is a brain condition that causes memory loss, confusion, and difficulty with thinking. It is the most common cause of dementia, a decline in mental ability severe enough to interfere with daily life. There is no cure for Alzheimer's, but treatments can help manage symptoms.

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Genetic polymorphisms

Variations in the DNA sequence among individuals.

Genetic polymorphisms are slight differences in a person's DNA sequence. These variations can influence how a person responds to medications, their risk for certain diseases, and other traits.

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Apolipoprotein E (ApoE)

A protein that helps transport fats in the blood.

ApoE is a protein involved in transporting fats (lipids) through the bloodstream. There are different versions (alleles) of ApoE, and some variations have been linked to an increased risk for Alzheimer's disease.

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Alleles

Different versions of a gene.

Alleles are alternative forms of a gene. For example, a gene for eye color might have alleles for blue eyes or brown eyes.

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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 a change in one of these building blocks, which can alter the protein's structure and function.

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ApoE2

A variant of the apolipoprotein E gene.

ApoE2 is one of three common variations (alleles) of the ApoE gene. Individuals with ApoE2 are often found to have a lower risk of developing Alzheimer's disease.

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ApoE4

A variant of the apolipoprotein E gene.

ApoE4 is a variant of the ApoE gene associated with an increased risk for Alzheimer's disease.