RESEARCH: ALZHEIMERS
FOLDING PROJECT #18224 PROFILE

This project looks at how changes in the ApoE protein affect Alzheimer's disease. Some ApoE versions (like ApoE2 and ApoE Christchurch) seem to protect against Alzheimer's, while others (like ApoE4) increase risk. By studying how these different ApoE versions move, scientists hope to understand how they contribute to Alzheimer's and develop 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. 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- Apolipoprotein E2, a slightly protective isoform of Apolipoprotein E with respect to Alzheimer's disease.

ApoE2 carriers have an increased risk of hyperproteinemia. p18221- Apolipoprotein E3(Serine).

Many of our experiments in the wet lab utilize this variant of E3 as it is chemically more ammenable to our studies.

We are exploring the impact of this experimental mutation on the underlying conformational ensemble of ApoE3 (p18219). p18222- Apolipoprotein E3, Christchurch (Serine).

Many of our experiments in the wet lab utilize this variant of E3 Christchurch as it is chemically more ammenable to our studies.

We are exploring the impact of this experimental mutation on the underlying conformational ensemble of ApoE3Ch (p18218). p18223- Apolipoprotein E2(Serine).

Many of our experiments in the wet lab utilize this variant of E2 as it is chemically more ammenable to our studies.

We are exploring the impact of this experimental mutation on the underlying conformational ensemble of ApoE2 (p18220).

Alzheimer's disease

A progressive neurodegenerative disorder characterized by memory loss and cognitive decline.

Alzheimer's disease is a serious brain condition that causes memory loss, thinking problems, and changes in behavior. 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 among individuals.

Genetic polymorphisms are variations in the DNA sequence that can occur between individuals. These variations can influence traits and disease susceptibility.

Apolipoprotein E (ApoE)

A protein that transports cholesterol and other lipids in the blood.

Apolipoprotein E (ApoE) is a crucial protein responsible for transporting fats and cholesterol throughout the body. It plays a role in various bodily functions, including lipid metabolism and brain health.

Alleles

Different versions of a gene.

Alleles are alternative forms of a 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.

An amino acid substitution is a modification in the protein structure where one amino acid is replaced by another. This change can affect the protein's function.

ApoE2 (R158C)

A specific variant of the ApoE gene associated with reduced risk of Alzheimer's disease.

ApoE2 (R158C) is a genetic variant of the Apolipoprotein E gene that has been linked to a decreased risk of developing Alzheimer's disease.

ApoE4 (C112R)

A specific variant of the ApoE gene associated with an increased risk of Alzheimer's disease.

ApoE4 (C112R) is a genetic variant of the Apolipoprotein E gene that significantly increases the likelihood of developing Alzheimer's disease.

ApoE3(Serine)

A specific variant of the ApoE gene commonly used in research.

ApoE3(Serine) is a common variation of the Apolipoprotein E gene often utilized in scientific studies.

Hyperproteinemia

A condition characterized by elevated levels of protein in the blood.

Hyperproteinemia is a medical condition where there is an abnormally high concentration of proteins in the blood. It can be caused by various factors.