Science journal: New research reveals why APOE4 increases the risk of Alzheimer's disease

News March 8, 2021 //--- The E4 allele (APOE4) of the apolipoprotein E gene (APOE) has been identified as a variety of diseases including cardiovascular disease and Alzheimer's disease (AD) The genetic risk factors of the disease, but the mechanism of action is still unclear.
APOE is a lipid transport protein, and lipid imbalance has recently become the main feature of several neurodegenerative diseases including AD.
However, it is not yet clear how APOE4 disrupts the lipid status in cells.

In a new study, researchers from the Massachusetts Institute of Technology and other research institutions used fibroblasts from APOE4 or APOE3 carriers to construct human induced pluripotent stem cells (iPSC), and then induced the differentiation of human iPSC to produce stars Based on this finding, the lipidome of astrocytes produced by human iPSC differentiation is destroyed by APOE4 instead of APOE3.
In addition, the lipidome of yeast cells expressing human APOE isoforms is also destroyed by APOE4.
APOE4 instead of APOE3 destroyed.
Related research results were recently published in the journal Science Translational Medicine, with the title of the paper "APOE4 disrupts intracellular lipid homeostasis in human iPSC-derived glia".

The picture comes from CC0 Public Domain.

These authors combined lipidomics and unbiased genome-wide screening for functional and genetic characterization in yeast, confirming that human APOE4 induces changes in lipid homeostasis.

Next, they identified the genetic and chemical regulators of this lipid destruction.
They found that in human iPSC-derived APOE4-expressing astrocytes and human APOE4-expressing yeast, the addition of choline (a soluble phospholipid precursor) to the culture medium can restore the cellular lipidome to their Basic state.

This study shed light on key molecular interferences in lipid metabolism that may lead to disease risks associated with the APOE4 genotype.
This study also shows that manipulation of lipid metabolism may be a treatment that can help reduce the risk of diseases associated with APOE4 alleles.
(Bioon.
com)

Reference: Grzegorz Sienski et al.