RESEARCH: ALZHEIMERS
FOLDING PROJECT #18218 PROFILE

Alzheimer's disease has no cure, but changes in a gene called ApoE can increase or decrease your risk. The project looks at how different versions of ApoE move around to understand how they might protect against or cause Alzheimer's. This could 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 is the most common cause of dementia, a general term for memory loss and other cognitive abilities severe enough to interfere with daily life.

Genetic polymorphisms

Variations in DNA sequence among individuals

Genetic polymorphisms are slight variations in the DNA sequence that occur naturally within a population. These variations can affect an individual's susceptibility to certain diseases, their response to medications, and other traits.

Apolipoprotein E (ApoE)

A protein that carries cholesterol and other fats in the blood

Apolipoprotein E (ApoE) is a crucial protein involved in transporting fats and cholesterol through the bloodstream. It also plays a role in brain health and repair.

Alleles

Different versions of a gene

Alleles are alternative forms of a gene that can occupy the same position (locus) on a chromosome. An individual inherits two alleles for each gene, one from each parent.

Amino acid substitution

A change in one amino acid in a protein sequence

Amino acid substitution refers to the replacement of one amino acid with another within a protein molecule. This change can alter the protein's structure and function.

ApoE3

A variant of apolipoprotein E

ApoE3 is the most common variant of apolipoprotein E. It carries a neutral risk for Alzheimer's disease.

ApoE2 (R158C)

A variant of apolipoprotein E with a specific amino acid substitution

ApoE2 (R158C) is a variant of apolipoprotein E associated with protection against Alzheimer's disease.

ApoE4 (C112R)

A variant of apolipoprotein E with a specific amino acid substitution

ApoE4 (C112R) is a variant of apolipoprotein E associated with an increased risk for Alzheimer's disease.

ApoEchristchurch (R136S)

A variant of apolipoprotein E with a specific amino acid substitution

ApoEchristchurch (R136S) is a recent variant of apolipoprotein E associated with protection against Alzheimer's disease.