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▎Editor of WuXi AppTec's content team Alzheimer's disease is the most common type of dementia in the elderly.
There are many factors that affect the occurrence of this neurological disease, including a person's genetic factors, daily diet, exercise and other lifestyles.
Studies in the past decades have found that in late-onset Alzheimer's disease, the APOE4 gene is one of the strongest genetic risk factors: more than half of patients carry this gene.
Recently, a study led by Professor Lihui Cai, a neuroscientist at the Massachusetts Institute of Technology (MIT) and a collaborator, gave us a new understanding of the role of the APOE4 gene in the development of Alzheimer's disease.
The researchers further discovered that the damage caused by this gene can be reversed by supplementing with an additional dietary supplement, choline, which is safe for humans.
Their research results were published in Science Translational Medicine, a sub-Journal of Science.
The APOE gene encodes apolipoprotein E, which is involved in lipid metabolism.
Among brain cells, astrocytes are the cell type that produces the most apolipoprotein E.
Therefore, in order to try to understand the impact of APOE4, the researchers designed an experiment to compare two types of astrocytes under in vitro culture conditions: their other genetic backgrounds are the same, only the version of the APOE gene is different, one It expresses APOE4, which increases the risk of Alzheimer's disease, and the other expresses APOE3-this version is the most common in the population, and it does not affect the risk of Alzheimer's disease.
It was found that just because of the different versions of the APOE gene, astrocytes showed significant differences in lipid processing.
Specifically, there are a lot of neutral lipids and cholesterol in APOE4 cells, accumulating more lipid droplets, and the triglycerides in them have much more unsaturated fatty acid chains than normal.
These results show that APOE4 makes the lipid state in glial cells out of balance.
"When the lipid balance is broken, many important cellular processes will be affected, such as intracellular transport, vesicle transport and endocytosis.
" Professor Cai Lihui explained, "Many basic functions of cells are therefore impaired.
"▲ Professor Lihui Cai, who led the research (picture source: MIT Laboratory homepage), "Lipid balance is necessary for cells to produce cell membranes and other normal functions, and it is also important for cells to respond to various stimuli.
These cells are in a state of high lipid imbalance.
, It will affect the stress response.
” Dr.
Julia Maeve Bonner, one of the lead authors of the study, added.
In order to find a corresponding method to help cells restore the important lipid metabolism balance, the researchers used yeast cells for systematic genetic screening in follow-up experiments.
This allowed them to discover that by supplementing choline to promote the synthesis of phospholipids (an important component of cell membranes), some of the damage suffered by cells can be reversed.
The experimental results in human glial cells further verified that after adding choline supplements to the culture medium, glial cells expressing APOE4 effectively reduced the accumulation of cholesterol and lipid droplets, and restored the lipid state of the cells.
normal.
Image source: 123RF "These results indicate that the regulation of lipid metabolism may be used as a treatment to help reduce the risk of diseases caused by APOE4 alleles.
" The study author concluded at the end of the abstract.
In fact, the choline supplemented to the cells in the experiment is an important nutrient that exists in many natural foods, such as egg yolks, meat, fish, as well as beans and nuts.
Professor Cai mentioned that the usual recommended minimum intake of choline is 550 mg per day for men and 425 mg per day for women, but many people may not have enough intake.
▲Choline is naturally present in many foods, and it can also be supplemented with dietary supplements (picture source: 123RF).
The researchers mentioned that there have been some previous studies involving the effects of choline supplementation on cognition, but the results of these trials were mixed.
The reason may be that these tests did not specifically target people with the APOE4 gene.
Therefore, the researchers plan to further verify whether choline supplementation can benefit those at high risk of disease carrying APOE4.
According to reports, the research team has begun to conduct research on mouse models of Alzheimer's disease.
These mice have the human APOE4 gene.
Researchers will test whether supplementation with choline can alleviate their disease symptoms.
"What we want to know is, if the amount of choline is adequately supplemented, will it ultimately help people with the APOE4 gene to delay the development of Alzheimer's disease and protect them.
"References[1] Grzegorz Sienski et al.
, (2021) APOE4 disrupts intracellular lipid homeostasis in human iPSC-derived glia.
Science Translational Medicine.
Doi: 10.
1126/scitranslmed.
aaz4564[2] Study offers an explanation for why the APOE4 gene enhances Alzheimer's risk.
Retrieved March.
9, 2021 from https://tsailaboratory.
mit.
edu/2021/03/05/study-offers-an-explanation-for-why-the-apoe4-gene-enhances-alzheimers-risk /[3] https://
There are many factors that affect the occurrence of this neurological disease, including a person's genetic factors, daily diet, exercise and other lifestyles.
Studies in the past decades have found that in late-onset Alzheimer's disease, the APOE4 gene is one of the strongest genetic risk factors: more than half of patients carry this gene.
Recently, a study led by Professor Lihui Cai, a neuroscientist at the Massachusetts Institute of Technology (MIT) and a collaborator, gave us a new understanding of the role of the APOE4 gene in the development of Alzheimer's disease.
The researchers further discovered that the damage caused by this gene can be reversed by supplementing with an additional dietary supplement, choline, which is safe for humans.
Their research results were published in Science Translational Medicine, a sub-Journal of Science.
The APOE gene encodes apolipoprotein E, which is involved in lipid metabolism.
Among brain cells, astrocytes are the cell type that produces the most apolipoprotein E.
Therefore, in order to try to understand the impact of APOE4, the researchers designed an experiment to compare two types of astrocytes under in vitro culture conditions: their other genetic backgrounds are the same, only the version of the APOE gene is different, one It expresses APOE4, which increases the risk of Alzheimer's disease, and the other expresses APOE3-this version is the most common in the population, and it does not affect the risk of Alzheimer's disease.
It was found that just because of the different versions of the APOE gene, astrocytes showed significant differences in lipid processing.
Specifically, there are a lot of neutral lipids and cholesterol in APOE4 cells, accumulating more lipid droplets, and the triglycerides in them have much more unsaturated fatty acid chains than normal.
These results show that APOE4 makes the lipid state in glial cells out of balance.
"When the lipid balance is broken, many important cellular processes will be affected, such as intracellular transport, vesicle transport and endocytosis.
" Professor Cai Lihui explained, "Many basic functions of cells are therefore impaired.
"▲ Professor Lihui Cai, who led the research (picture source: MIT Laboratory homepage), "Lipid balance is necessary for cells to produce cell membranes and other normal functions, and it is also important for cells to respond to various stimuli.
These cells are in a state of high lipid imbalance.
, It will affect the stress response.
” Dr.
Julia Maeve Bonner, one of the lead authors of the study, added.
In order to find a corresponding method to help cells restore the important lipid metabolism balance, the researchers used yeast cells for systematic genetic screening in follow-up experiments.
This allowed them to discover that by supplementing choline to promote the synthesis of phospholipids (an important component of cell membranes), some of the damage suffered by cells can be reversed.
The experimental results in human glial cells further verified that after adding choline supplements to the culture medium, glial cells expressing APOE4 effectively reduced the accumulation of cholesterol and lipid droplets, and restored the lipid state of the cells.
normal.
Image source: 123RF "These results indicate that the regulation of lipid metabolism may be used as a treatment to help reduce the risk of diseases caused by APOE4 alleles.
" The study author concluded at the end of the abstract.
In fact, the choline supplemented to the cells in the experiment is an important nutrient that exists in many natural foods, such as egg yolks, meat, fish, as well as beans and nuts.
Professor Cai mentioned that the usual recommended minimum intake of choline is 550 mg per day for men and 425 mg per day for women, but many people may not have enough intake.
▲Choline is naturally present in many foods, and it can also be supplemented with dietary supplements (picture source: 123RF).
The researchers mentioned that there have been some previous studies involving the effects of choline supplementation on cognition, but the results of these trials were mixed.
The reason may be that these tests did not specifically target people with the APOE4 gene.
Therefore, the researchers plan to further verify whether choline supplementation can benefit those at high risk of disease carrying APOE4.
According to reports, the research team has begun to conduct research on mouse models of Alzheimer's disease.
These mice have the human APOE4 gene.
Researchers will test whether supplementation with choline can alleviate their disease symptoms.
"What we want to know is, if the amount of choline is adequately supplemented, will it ultimately help people with the APOE4 gene to delay the development of Alzheimer's disease and protect them.
"References[1] Grzegorz Sienski et al.
, (2021) APOE4 disrupts intracellular lipid homeostasis in human iPSC-derived glia.
Science Translational Medicine.
Doi: 10.
1126/scitranslmed.
aaz4564[2] Study offers an explanation for why the APOE4 gene enhances Alzheimer's risk.
Retrieved March.
9, 2021 from https://tsailaboratory.
mit.
edu/2021/03/05/study-offers-an-explanation-for-why-the-apoe4-gene-enhances-alzheimers-risk /[3] https://
