RESEARCH: ALZHEIMERS
FOLDING PROJECT #18220 PROFILE

This project looks at how different versions of the ApoE protein affect Alzheimer's disease risk. Some versions, like ApoE2 and ApoE Christchurch, seem to protect against the disease, while others, like ApoE4, increase risk. Scientists are using computer simulations to understand how these different versions work and hope this will lead to 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. P18215- Apolipoprotein E4, highly associated with Alzheimer's disease severity and early onset. p18218- Apolipoprotein E3, Christchurch.

A rare isoform of ApoE which seems to be protective from familial Alzheimer's disease. p18219- Apolipoprotein E3, The most common isoform of ApoE.

Risk neutral for Alzheimer's disease and the baseline comparator for our studies. p18220 (In preparation) - Apolipoprotein E2, a slightly protective isoform of Apolipoprotein E with respect to Alzheimer's disease.

ApoE2 carriers have an increased risk of hyperproteinemia.

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 sequences.

Genetic polymorphisms are variations in the DNA sequence that occur between individuals. These variations can affect how genes are expressed and contribute to differences in traits and disease susceptibility.

Apolipoprotein E (ApoE)

Apolipoprotein E

Apolipoprotein E is a protein that plays a crucial role in lipid metabolism. It helps transport fats and cholesterol through the bloodstream and also interacts with cells in the brain.

Alleles

Different versions of a gene.

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

Amino Acid Substitution

Replacement of one amino acid with another in a protein.

Amino acid substitution is a change in the sequence of amino acids that make up a protein. These changes can affect the protein's structure and function.

ApoE3

Apolipoprotein E3

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

ApoE2

Apolipoprotein E2

ApoE2 is a variant of apolipoprotein E that appears to be slightly protective against Alzheimer's disease.

ApoE4

Apolipoprotein E4

ApoE4 is a variant of apolipoprotein E that is strongly associated with an increased risk of Alzheimer's disease.

ApoE Christchurch

Apolipoprotein E Christchurch variant

ApoE Christchurch is a rare variant of apolipoprotein E that has been associated with protection against Alzheimer's disease.

Hyperproteinemia

High levels of protein in the blood.

Hyperproteinemia is a condition characterized by elevated levels of protein in the blood. It can be caused by various factors, including dehydration and certain liver diseases.