Summary of APOE
Apolipoprotein E (APOE) transports fat-soluble vitamins and cholesterol into the lymph system and then into the blood. APOE has been shown to reduce cholesterol levels, reduce the risk of heart disease, and reduce inflammation [R][R][R].
There are at least three slightly different versions (alleles) of the APOE gene. The major alleles are called e2, e3, and e4. The most common allele is e3, which is found in more than half of the general population.
rs429358(C;C) + rs7412 (C;C) = APOE4/APOE4 (Bad) = 12x for late-onset Alzheimer's and 61x for early-onset disease [R].
rs429358(C;T) + rs7412 (C;C) = APOE3/APOE4 (Bad) = >3x increased risk for Alzheimer's; 1.4x increased risk for heart disease [R].
rs429358(T;T) + rs7412 (C;C) = APOE3/APOE3 (Good) -- most common
rs429358(T;T) + rs7412 (C;T) = APOE2/APOE3 (Good)
rs429358(T;T) + rs7412 (T;T) = APOE2/APOE2 (Good) -- lowest risk
Certain APOE varieties may lead to increased risk of heart disease, high cholesterol, inflammation, depression and cancer [R]. In particular, the APOE4 variety cannot accomplish the beneficial functions as well that the other varieties can do. People with two APOE4 alleles are 20X more likely to get Alzheimer's.
- Low APOE results in higher cholesterol.
- Low APOE causes increased oxidative stress, inflammation.
- Low APOE is most notably a causal factor in Alzheimer’s.
APOE is anti-inflammatory. It suppresses T cell proliferation, macrophage functioning regulation, natural killer T cell activation and overall decreases inflammation and oxidation.
APOE helps break down the amyloid beta that is believed to contribute to Alzheimer's.
- Cholesterol levels: APOE participates in cholesterol redistribution from cells with excess cholesterol to those requiring it, thus reducing cholesterol levels [R].
- Prevents Atherosclerosis (cardiovascular disease): In a study done on mice that were missing the APOE gene, it was showed that people with APOE4 had a higher risk of getting atherosclerosis, a disease where plaque is built up in the arteries [R].
- Inflammation: APOE reduces the risk to develop age-related macular degeneration and inflammation [R].
- Sleep disturbances (snoring, sleep apnea): APOE decreased problems in snoring and sleep apnea (in adults without dementia) [R].
- Alzheimer’s: APOE2 can serve a protective role in fighting against Alzheimer’s [R], while th APOE4 variant is a large risk factor for late-onset Alzheimer’s Disease [R].
- Weight Management: APOE3 more efficiently harvests dietary energy and deposits fat in fat tissue compared to APOE4 [R].
- Fatigue: APOE4 gene is associated with fatigue in people who had minor brain injuries [R].
- Depression: High APOE4 levels lead to depression in people with Alzheimer’s Disease [R].
- Migraines: APOE4 was positively linked to headaches [R].
- Brain Hemorrhages: APOE interacts with lipid levels in the brain to play a role in causing brain hemorrhages [R].
- Cancer (renal cell carcinoma and colon adenocarcinoma): Interactions between APOE and other genes are related to higher cancer susceptibility [R].
APOE gene variants have also been studied as a potential risk factor for age-related macular degeneration, an eye disease that is a leading cause of vision loss among older people worldwide. Some studies have suggested that having at least one copy of the APOE e4 allele may help protect against this disease or delay the onset of vision loss, while having at least one copy of the APOE e2 allele may increase the risk of this disease or cause symptoms to appear earlier.
APOE is synthesized principally in the liver, and can bind to the LDL receptor.
Recommended name:Apolipoprotein E
- RS1065853 (APOE) ??
- RS405509 (APOE) ??
- RS429358 (APOE) ??
- RS438811 (APOE) ??
- RS439401 (APOE) ??
- RS440446 (APOE) ??
- RS445925 (APOE) ??
- RS449647 (APOE) ??
- RS7412 (APOE) ??
- RS769449 (APOE) ??
- RS769452 (APOE) ??
- RS769455 (APOE) ??
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Top Gene-Substance Interactions
APOE Interacts with These Diseases
If you have an APOE variety that doesn't work as well (APOE4), you can do a number of things to increase its production or function. You should be promoting the following:
- Education: More years of education meant higher levels of APOE [R].
- Mental Exercises: Daily mental exercises (puzzles, reading, etc.) help stabilize APOE levels and prevent the decline of brain function [R].
- Diets High in Polyunsaturated Fats and Low in Carbohydrates: Such as the Mediterannian diet or Ketogenic diet [R].
- Lowering Cholesterol [R]- lowering serum cholesterol levels may reduce a person’s risk for Alzheimer’s disease, even if they have two ApoE4 alleles, thus reducing the risk from nine or ten times the odds of getting Alzheimer's down to just two times the odds.
- Cold Showers
- Fish oil/DHA
- Vitamin A/Retinol
APOE is decreased by inflammation but increased by TGF-beta.
Substances That Increase APOE
Substances That Decrease APOE
Conditions with Increased Gene Activity
|Condition||Change (log2fold)||Comparison||Species||Experimental variables||Experiment name|
Conditions with Decreased Gene Activity
|Condition||Change (log2fold)||Comparison||Species||Experimental variables||Experiment name|
The following transcription factors affect gene expression:
Occurs in all lipoprotein fractions in plasma. It constitutes 10-20% of very low density lipoproteins (VLDL) and 1-2% of high density lipoproteins (HDL). APOE is produced in most organs. Significant quantities are produced in liver, brain, spleen, lung, adrenal, ovary, kidney and muscle.
- Beta-Amyloid Binding
- Lipid Transporter Activity
- Phospholipid Binding
- Heparin Binding
- Lipid Binding
- Cholesterol Binding
- Antioxidant Activity
- Cholesterol Transporter Activity
- Identical Protein Binding
- Protein Homodimerization Activity
- Metal Chelating Activity
- Tau Protein Binding
- Low-Density Lipoprotein Particle Receptor Binding
- Phosphatidylcholine-Sterol O-Acyltransferase Activator Activity
- Very-Low-Density Lipoprotein Particle Receptor Binding
- Lipoprotein Particle Binding
- Ampa Glutamate Receptor Clustering
- Artery Morphogenesis
- Cellular Calcium Ion Homeostasis
- Cgmp-Mediated Signaling
- Cholesterol Catabolic Process
- Cholesterol Efflux
- Cholesterol Homeostasis
- Cholesterol Metabolic Process
- Chylomicron Remnant Clearance
- Cytoskeleton Organization
- Fatty Acid Homeostasis
- G-Protein Coupled Receptor Signaling Pathway
- High-Density Lipoprotein Particle Assembly
- High-Density Lipoprotein Particle Clearance
- High-Density Lipoprotein Particle Remodeling
- Intracellular Transport
- Lipid Transport Involved In Lipid Storage
- Lipoprotein Biosynthetic Process
- Lipoprotein Catabolic Process
- Lipoprotein Metabolic Process
- Long-Chain Fatty Acid Transport
- Low-Density Lipoprotein Particle Remodeling
- Maintenance Of Location In Cell
- Negative Regulation Of Beta-Amyloid Formation
- Negative Regulation Of Blood Coagulation
- Negative Regulation Of Blood Vessel Endothelial Cell Migration
- Negative Regulation Of Canonical Wnt Signaling Pathway
- Negative Regulation Of Cholesterol Biosynthetic Process
- Negative Regulation Of Cholesterol Efflux
- Negative Regulation Of Dendritic Spine Development
- Negative Regulation Of Dendritic Spine Maintenance
- Negative Regulation Of Endothelial Cell Proliferation
- Negative Regulation Of Inflammatory Response
- Negative Regulation Of Lipid Biosynthetic Process
- Negative Regulation Of Lipid Transport Across Blood Brain Barrier
- Negative Regulation Of Map Kinase Activity
- Negative Regulation Of Neuron Apoptotic Process
- Negative Regulation Of Neuron Death
- Negative Regulation Of Phospholipid Efflux
- Negative Regulation Of Platelet Activation
- Negative Regulation Of Postsynaptic Membrane Organization
- Negative Regulation Of Presynaptic Membrane Organization
- Neuron Projection Regeneration
- Nitric Oxide Mediated Signal Transduction
- Nmda Glutamate Receptor Clustering
- Phospholipid Efflux
- Positive Regulation By Host Of Viral Process
- Positive Regulation Of Beta-Amyloid Formation
- Positive Regulation Of Cgmp Biosynthetic Process
- Positive Regulation Of Cholesterol Efflux
- Positive Regulation Of Cholesterol Esterification
- Positive Regulation Of Dendritic Spine Development
- Positive Regulation Of Dendritic Spine Maintenance
- Positive Regulation Of Lipid Biosynthetic Process
- Positive Regulation Of Lipid Transport Across Blood Brain Barrier
- Positive Regulation Of Low-Density Lipoprotein Particle Receptor Catabolic Process
- Positive Regulation Of Membrane Protein Ectodomain Proteolysis
- Positive Regulation Of Neurofibrillary Tangle Assembly
- Positive Regulation Of Neuron Death
- Positive Regulation Of Nitric-Oxide Synthase Activity
- Positive Regulation Of Phospholipid Efflux
- Positive Regulation Of Postsynaptic Membrane Organization
- Positive Regulation Of Presynaptic Membrane Organization
- Protein Import
- Receptor-Mediated Endocytosis
- Regulation Of Axon Extension
- Regulation Of Beta-Amyloid Clearance
- Regulation Of Cdc42 Protein Signal Transduction
- Regulation Of Gene Expression
- Regulation Of Neuronal Synaptic Plasticity
- Regulation Of Neuron Death
- Regulation Of Tau-Protein Kinase Activity
- Response To Dietary Excess
- Response To Reactive Oxygen Species
- Retinoid Metabolic Process
- Reverse Cholesterol Transport
- Synaptic Transmission, Cholinergic
- Triglyceride Catabolic Process
- Triglyceride Homeostasis
- Triglyceride Metabolic Process
- Very-Low-Density Lipoprotein Particle Clearance
- Very-Low-Density Lipoprotein Particle Remodeling
- Virion Assembly
- Human Serum Albumin
- Serum Albumin Iodonated