RESEARCH: ALZHEIMERS
FOLDING PROJECT #18210 PROFILE

Alzheimer's is a deadly disease with no cure. Changes in the ApoE gene affect risk. Some versions protect against Alzheimer's, while others increase risk. This project uses computer simulations to understand how different ApoE versions work, hoping to find new treatments for 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 characterized by cognitive decline.

Alzheimer's disease is a serious brain disorder that slowly destroys memory and thinking skills. It is the most common cause of dementia, a general term for memory loss and other intellectual abilities severe enough to interfere with daily life. There are currently no cures for Alzheimer's disease, but treatments can help manage symptoms.

Genetic polymorphisms

Variations in DNA sequences among individuals.

Genetic polymorphisms are variations in the DNA sequence that occur naturally between people. These variations can affect a person's susceptibility to certain diseases, their response to medications, and other traits.

Apolipoprotein E (ApoE)

A lipoprotein that transports cholesterol and other lipids in the bloodstream.

ApoE is a protein found in the blood that helps transport fats and cholesterol. It has different versions (alleles) that can affect a person's risk for developing Alzheimer's disease.

Alleles

Different versions of a gene.

Alleles are different forms of the same gene. Each person inherits two alleles for each gene, one from their mother and one from their father.

Amino acid substitution

A change in one amino acid in a protein sequence.

Amino acid substitution is a change in the building blocks of a protein. These changes can affect how a protein functions.

ApoE4

A genetic variant of apolipoprotein E associated with an increased risk of Alzheimer's disease.

ApoE4 is a specific version of the ApoE gene that has been linked to a higher risk of developing Alzheimer's disease.

ApoE2

A genetic variant of apolipoprotein E associated with a decreased risk of Alzheimer's disease.

ApoE2 is a specific version of the ApoE gene that appears to lower the risk of developing Alzheimer's disease.

ApoE3

The most common variant of apolipoprotein E.

ApoE3 is the most prevalent version of the ApoE gene and generally carries a neutral risk for Alzheimer's disease.

ApoE Christchurch

A recent variant of apolipoprotein E associated with a decreased risk of Alzheimer's disease.

ApoE Christchurch is a relatively new variation of the ApoE gene that appears to protect against Alzheimer's disease.