RESEARCH: ALZHEIMERS
FOLDING PROJECT #18219 PROFILE

Alzheimer's is a serious disease with no cures. Some genes, like ApoE, strongly influence whether you get it. Different versions of ApoE protect or increase your risk. This project uses computer simulations to understand how these different versions work and hopefully 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 disease.

Alzheimer's disease is a brain disorder that slowly destroys memory and thinking skills. It's the most common cause of dementia, a general term for memory loss and other intellectual abilities severe enough to interfere with daily life.

Genetic polymorphisms

Variations in DNA sequences among individuals.

Genetic polymorphisms are slight differences in our DNA sequence. These variations can affect how our bodies function and our susceptibility to certain diseases.

Apolipoprotein E (ApoE)

ApoE: A protein involved in lipid transport.

Apolipoprotein E (ApoE) is a protein that plays a crucial role in transporting fats (lipids) throughout the body. It's found in the blood and brain, and variations in ApoE genes can influence our risk for diseases like Alzheimer's.

Alleles

Alternative forms of a gene.

Alleles are different versions of the same gene. We inherit two alleles for each gene, one from our mother and one from our father. These variations can lead to different traits.

Amino acid

Building blocks of proteins.

Amino acids are the fundamental units that make up proteins. There are 20 different types of amino acids, and they are linked together in specific sequences to form unique proteins with diverse functions.

ApoE2

A variant of apolipoprotein E.

ApoE2 is a variant of the ApoE protein. Some studies suggest that individuals carrying two copies of the ApoE2 allele may have a reduced risk of developing Alzheimer's disease.

ApoE4

A variant of apolipoprotein E.

ApoE4 is a variant of the ApoE protein. Individuals carrying one or two copies of the ApoE4 allele have an increased risk of developing Alzheimer's disease.

ApoEchristchurch

A variant of apolipoprotein E.

ApoE Christchurch is a recently discovered variant of the ApoE protein. Studies suggest that it may offer some protection against Alzheimer's disease.