Vince
Super Moderator
Apolipoprotein-E (ApoE) is composed of 299 amino acids and transports lipoproteins, fat-soluble vitamins, and cholesterol into the lymph system and then into the blood. It is synthesized principally in the liver, but has also been found in other tissues such as the brain, kidneys, and spleen. In the nervous system, non-neuronal cell types, most notably astroglia and mocroglia, are the primary producers of ApoE, while neurons preferentially express the receptors for ApoE. There are seven currently identified mammalian receptors for ApoE which belong to the evolutionarily conserved low density lipoprotein receptor gene family.
People with harmful forms of the ApoE gene (genotype 3/4, 4/4) have up to 12 times the risk of developing Alzheimer's disease compared with those who have other variations (2/2, 2/3, 3/3) of the gene. For years, researchers have thought that the ApoE gene increased Alzheimer's risk by producing a protein that binds to amyloid beta. Scientists thought that this bond could make it easier for plaques to form.
Recent research indicates that ApoE does not appear to bind to amyloid beta, but to a receptor in astrocytes. "Studies by other researchers have shown that astrocytes can degrade amyloid beta," Dr. Verghese said. "The receptor we identified may be important for getting amyloid beta into the astrocyte so it can be broken down. It's possible that when the harmful forms of ApoE bind to the receptor, this reduces the opportunities for amyloid to be degraded." The researchers are planning follow-up studies of the effects of ApoE-blocking treatments in mice.
Another role of ApoE is in the removal of mercury from the biosystem. ApoE 2 codes for cysteine at amino acid positions 112 and 158, whereas, ApoE 3 codes for a cysteine at position 112, but an arginine at position 158. ApoE 4 codes for an arginine at both positions 112 and 158. Cysteine binds mercury, arginine does not. Therefore, the best genotype for removing mercury via this system is an ApoE 2/2 (4 cysteine residues), vs. an ApoE 3/3 (the highest incidence in the human population, 2 cysteine residues and 2 arginine residues), vs. the worst ApoE 4/4 (4 arginines and no mercury removing capability).
Apolipoprotein-E genotyping has been investigated as an indicator of susceptibility to heavy metal neurotoxicity
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People with harmful forms of the ApoE gene (genotype 3/4, 4/4) have up to 12 times the risk of developing Alzheimer's disease compared with those who have other variations (2/2, 2/3, 3/3) of the gene. For years, researchers have thought that the ApoE gene increased Alzheimer's risk by producing a protein that binds to amyloid beta. Scientists thought that this bond could make it easier for plaques to form.
Recent research indicates that ApoE does not appear to bind to amyloid beta, but to a receptor in astrocytes. "Studies by other researchers have shown that astrocytes can degrade amyloid beta," Dr. Verghese said. "The receptor we identified may be important for getting amyloid beta into the astrocyte so it can be broken down. It's possible that when the harmful forms of ApoE bind to the receptor, this reduces the opportunities for amyloid to be degraded." The researchers are planning follow-up studies of the effects of ApoE-blocking treatments in mice.
Another role of ApoE is in the removal of mercury from the biosystem. ApoE 2 codes for cysteine at amino acid positions 112 and 158, whereas, ApoE 3 codes for a cysteine at position 112, but an arginine at position 158. ApoE 4 codes for an arginine at both positions 112 and 158. Cysteine binds mercury, arginine does not. Therefore, the best genotype for removing mercury via this system is an ApoE 2/2 (4 cysteine residues), vs. an ApoE 3/3 (the highest incidence in the human population, 2 cysteine residues and 2 arginine residues), vs. the worst ApoE 4/4 (4 arginines and no mercury removing capability).
Apolipoprotein-E genotyping has been investigated as an indicator of susceptibility to heavy metal neurotoxicity
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