RESEARCH: ALZHEIMERS
FOLDING PROJECT #18221 PROFILE

This project looks at how different versions of a protein called ApoE affect Alzheimer's disease. Some ApoE versions protect against Alzheimer's, while others increase the risk. Scientists are using computer simulations to understand how these different versions work and hope to develop 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- 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 ApoE.

Alzheimer's disease

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

Alzheimer's disease is a serious 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 cognitive abilities severe enough to interfere with daily life.

Apolipoprotein E

A protein that plays a role in lipid transport in the blood.

Apolipoprotein E (ApoE) is a crucial protein found in the blood. It helps transport fats throughout the body. There are different versions (alleles) of ApoE, some linked to increased or decreased risk for Alzheimer's disease.

ApoE3

A common variant of ApoE associated with neutral risk for Alzheimer's disease.

ApoE3 is the most prevalent version of the ApoE protein. People with this allele generally have a normal risk of developing Alzheimer's disease.

ApoE4

A variant of ApoE strongly associated with increased risk for Alzheimer's disease.

ApoE4 is a variant of the ApoE protein that significantly raises the likelihood of developing Alzheimer's disease. People carrying this allele have a much higher chance of experiencing the condition.

ApoE2

A variant of ApoE associated with a slightly reduced risk for Alzheimer's disease.

ApoE2 is another version of the ApoE protein. While it doesn't completely prevent Alzheimer's disease, individuals carrying this allele tend to have a lower risk compared to those with other variants.

ApoE Christchurch

A rare variant of ApoE3 associated with protection against Alzheimer's disease.

ApoE Christchurch is a unique variation of the ApoE3 protein. Studies suggest that individuals with this variant may be less susceptible to developing Alzheimer's disease.

P18215

Apolipoprotein E4

P18215 is a protein identification code in the database system Entrez Gene. It specifically refers to Apolipoprotein E4.

P18216

Apolipoprotein E2

P18216 is a protein identification code in the database system Entrez Gene. It specifically refers to Apolipoprotein E2.

P18217

Apolipoprotein E3

P18217 is a protein identification code in the database system Entrez Gene. It specifically refers to Apolipoprotein E3.

P18218

Apolipoprotein E3(Serine)

P18218 is a protein identification code in the database system Entrez Gene. It specifically refers to Apolipoprotein E3 with a serine amino acid at a specific position.