Summary of APOE
The APOE gene codes for apolipoprotein E (apoE). ApoE helps remove fats such as triglycerides and cholesterol from the blood [R].
ApoE is also involved in the breakdown and aggregation of the protein beta-amyloid. Beta-amyloid has been implicated in the development of Alzheimer’s disease [R].
rs429358 and rs7412 are two SNPs that form three major alleles. These alleles form apoE proteins (isoforms) that differ in ability to clear fats and regulate beta-amyloid [R]:
- The apoE3 isoform (encoded by the e3 allele) is produced from a ‘T’ at rs429358 and a ‘C’ at rs7412. This isoform is effective at clearing fats and regulating beta-amyloid.
- The apoE2 isoform (encoded by the e2 allele) is produced from a ‘T’ at both rs429358 and rs7412. This isoform is more effective than apoE3 at clearing fats and regulating beta-amyloid.
- The apoE4 isoform (encoded by the e4 allele) is produced from a ‘C’ at both rs429358 and rs7412. This isoform is less effective than apoE2 and apoE3 at clearing fats and regulating beta-amyloid.
apoE2 isoforms may contribute to [R, R, R, R]:
- Normal cholesterol levels
- Weight management
- Protection against late-onset Alzheimer’s disease
- Age-related macular (part of eye) degeneration
Conversely, apoE4 isoforms have been linked to [R, R, R, R, R, R]:
- High cholesterol
- Heart disease
- Migraines
- Depression
- Late-onset Alzheimer’s disease
- Lower odds of snoring and sleep apnea
Potential isoform genotypes are as follows [R]:
- e4 / e4: rs429358-CC and rs7412-CC
- e3 / e4: rs429358-TC and rs7412-CC
- e2 / e4: rs429358-TC and rs7412-TC
- e3 / e3: rs429358-TT and rs7412-CC
- e2 / e3: rs429358-TT and rs7412-TC
- e2 / e2: rs429358-TT and rs7412-TT
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Protein names
Recommended name:
Apolipoprotein EAlternative name(s):
Apo-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
| Disease | Score |
Fixes
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
- Curcumin
- Butyrate
APOE is decreased by inflammation but increased by TGF-beta.
Substances That Increase APOE
| Substances | Interaction | Organism | Category |
Substances That Decrease APOE
| Substances | Interaction | Organism | Category |
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 |
|---|
Technical
The following transcription factors affect gene expression:
Tissue specificity:
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.
Gene Pathways:
Molecular Function:
- 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
Biological Processes:
- Response To Reactive Oxygen Species
- Retinoid Metabolic Process
- Negative Regulation Of Endothelial Cell Proliferation
- Response To Dietary Excess
- Triglyceride Metabolic Process
- Cholesterol Catabolic Process
- Cellular Calcium Ion Homeostasis
- Receptor-Mediated Endocytosis
- Cytoskeleton Organization
- G-Protein Coupled Receptor Signaling Pathway
- Nitric Oxide Mediated Signal Transduction
- Synaptic Transmission, Cholinergic
- Cholesterol Metabolic Process
- Regulation Of Gene Expression
- Negative Regulation Of Platelet Activation
- Positive Regulation Of Cholesterol Esterification
- Positive Regulation Of Cholesterol Efflux
- Lipid Transport Involved In Lipid Storage
- Long-Chain Fatty Acid Transport
- Protein Import
- Virion Assembly
- Triglyceride Catabolic Process
- Cgmp-Mediated Signaling
- Negative Regulation Of Blood Coagulation
- Regulation Of Axon Extension
- Positive Regulation Of Cgmp Biosynthetic Process
- Neuron Projection Regeneration
- Regulation Of Cdc42 Protein Signal Transduction
- Positive Regulation Of Low-Density Lipoprotein Particle Receptor Catabolic Process
- Cholesterol Efflux
- Phospholipid Efflux
- Very-Low-Density Lipoprotein Particle Remodeling
- Low-Density Lipoprotein Particle Remodeling
- High-Density Lipoprotein Particle Remodeling
- High-Density Lipoprotein Particle Assembly
- Chylomicron Remnant Clearance
- High-Density Lipoprotein Particle Clearance
- Very-Low-Density Lipoprotein Particle Clearance
- Lipoprotein Metabolic Process
- Lipoprotein Biosynthetic Process
- Lipoprotein Catabolic Process
- Vasodilation
- Cholesterol Homeostasis
- Negative Regulation Of Map Kinase Activity
- Negative Regulation Of Neuron Apoptotic Process
- Negative Regulation Of Blood Vessel Endothelial Cell Migration
- Reverse Cholesterol Transport
- Positive Regulation By Host Of Viral Process
- Negative Regulation Of Cholesterol Biosynthetic Process
- Positive Regulation Of Lipid Biosynthetic Process
- Intracellular Transport
- Regulation Of Neuronal Synaptic Plasticity
- Artery Morphogenesis
- Negative Regulation Of Inflammatory Response
- Positive Regulation Of Nitric-Oxide Synthase Activity
- Positive Regulation Of Membrane Protein Ectodomain Proteolysis
- Negative Regulation Of Lipid Biosynthetic Process
- Maintenance Of Location In Cell
- Fatty Acid Homeostasis
- Positive Regulation Of Dendritic Spine Development
- Negative Regulation Of Dendritic Spine Development
- Triglyceride Homeostasis
- Negative Regulation Of Canonical Wnt Signaling Pathway
- Negative Regulation Of Cholesterol Efflux
- Ampa Glutamate Receptor Clustering
- Nmda Glutamate Receptor Clustering
- Regulation Of Beta-Amyloid Clearance
- Regulation Of Neuron Death
- Negative Regulation Of Neuron Death
- Positive Regulation Of Neuron Death
- Negative Regulation Of Postsynaptic Membrane Organization
- Positive Regulation Of Postsynaptic Membrane Organization
- Negative Regulation Of Presynaptic Membrane Organization
- Positive Regulation Of Presynaptic Membrane Organization
- Positive Regulation Of Beta-Amyloid Formation
- Negative Regulation Of Beta-Amyloid Formation
- Regulation Of Tau-Protein Kinase Activity
- Negative Regulation Of Dendritic Spine Maintenance
- Positive Regulation Of Dendritic Spine Maintenance
- Positive Regulation Of Phospholipid Efflux
- Positive Regulation Of Neurofibrillary Tangle Assembly
- Negative Regulation Of Phospholipid Efflux
- Negative Regulation Of Lipid Transport Across Blood Brain Barrier
- Positive Regulation Of Lipid Transport Across Blood Brain Barrier
Drug Bank:
- Human Serum Albumin
- Serum Albumin Iodonated