RESEARCH: ALZHEIMERS
FOLDING PROJECT #18213 PROFILE

This project studies ApoE protein changes linked to Alzheimer's disease. Some ApoE versions protect against Alzheimer's, while others increase risk. Scientists use computer simulations and lab experiments to understand how these ApoE changes work and hope to develop new treatments for Alzheimer's.

Note: This TLDR is a simplication and may not be 100% accurate.

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.

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. In other p182XX projects we have simulated ApoE variants to try to understand the conformations that ApoE adopts in solution.

We are also working to verify these findings in the laboratory.

To do this, we must introduce some additional mutations to ApoE to enable it's study.

To ensure our experimental and simulation results agree, we are also simulating ApoE with the mutations required to perform our experiments. As a whole, we hope the simulations of p182XX lead to a better understanding of how ApoE contributes to Alzheimer's disease.

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Alzheimer's disease

A neurodegenerative disease characterized by memory loss and cognitive decline.

Alzheimer's disease is a progressive brain disorder that slowly destroys memory and thinking skills. It is the most common cause of dementia, affecting millions worldwide.

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Genetic polymorphisms

Variations in DNA sequences among individuals.

Genetic polymorphisms are differences in DNA sequences that can affect how our bodies function. These variations can lead to different traits and susceptibilities to diseases.

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Apolipoprotein E (ApoE)

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

ApoE is a crucial protein involved in transporting fats (lipids) throughout the body. It plays a vital role in cholesterol metabolism and can influence the development of certain diseases.

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Amino acids

Building blocks of proteins.

Amino acids are the fundamental units that make up proteins. They link together in chains to form complex structures essential for various biological processes.

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Alleles

Different versions of a gene.

Alleles are variations within a gene. For example, a gene for eye color might have alleles for blue eyes, brown eyes, or green eyes.

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ApoE2

A variant of the ApoE protein.

ApoE2 is a specific version of the ApoE protein. Research suggests that individuals with this variant may have a reduced risk of developing Alzheimer's disease.

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ApoE4

A variant of the ApoE protein.

ApoE4 is a specific version of the ApoE protein. Studies have shown that individuals with this variant are at an increased risk of developing Alzheimer's disease.

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Mutations

Changes in the DNA sequence.

Mutations are alterations in the genetic code. They can be inherited or occur spontaneously and may lead to changes in protein function or disease development.

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Therapeutics

Medical treatments intended to prevent or cure disease.

Therapeutics encompass a wide range of medical interventions designed to treat diseases. This includes medications, therapies, and surgical procedures.