Alzheimer’s disease prevalence and deaths are on the rise, claiming over 6,000 lives in the USA every week. Yet many people don’t even know their APOE genotype which arguably has the biggest impact on future Alzheimer’s disease and dementia as well as cardiovascular disease risk.
In this show we dive deeper into what the APOE gene is and how you can tweak your lifestyle to reduce your risk of future disease—especially if you have one or two copies of the APOE ε4 gene.
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00:53 APOE is a gene that makes proteins that are involved in lipid binding. It is the predominant cholesterol transport protein in the brain.
01:10 APOE binds and interacts with inflammatory components like lipopolysaccharides and amyloid beta. It is believed to facilitate the clearance of inflammatory pathogenic molecules. This means that APO may have a role in innate immunity.
01:39 APOE 4 on two alleles increases risk of Alzheimer’s disease by up to 15-fold. One copy of the gene represents a 2 to 3-fold increased risk.
03:13 There are 3 different APOE isoforms: APOE2, APOE3, APOE4 allele. The APOE2 has nearly neutral risk. APOE3 is moderate. APOE4 allele has greater risk, especially if you have 2 copies.
03:44 Having the gene does not mean that you will get the disease. Genes load the gun. Your environment pulls the trigger.
04:35 APOE is involved in lipid metabolism. It is co-secreted in the liver with VLDL lipoprotein (very low-density lipoprotein). It is made in the small intestine and co-secreted with chylomicrons. It is synthesized and combined in the liver with APOE. During circulation, VLDL and chylomicrons become enriched in APOE.
05:30 Lipoproteins shuttle lipids and cholesterol from the gut to the peripheral part of the body. HDL is involved in the reverse cholesterol transport.
06:05 APOE can redistribute lipids across tissues and cell types. It facilitates the absorption of triglycerides and cholesterol. APOE interacts with LDL receptors and regulate the levels of LDL and VLDL. It is involved in the catabolism of lipids and the anabolism of lipids.
07:40 APOE is secreted by the liver with VLDL and bile acids. In the capillaries, lipoprotein lipase releases APOE from free fatty acids for the distribution of them to peripheral cells.
08:00 Lipoprotein lipase facilitates your metabolic deposits. Hormone sensitive lipase facilitates your metabolic withdrawals. In a high insulin environment, you will find increased levels of lipoprotein lipase. In a low insulin environment, facilitates the increase of hormone-sensitive lipase, liberating stored energy.
09:42 Increasing your omega 3 index with omega 3 fats from fish in the diet and dietary supplements has been shown to enhance protection for individuals who have 1 or more allele of APE 4 isoform. A low omega 3 index is linked with various diseases.
11:35 APOE4 isoforms differentially effect blood lipid profiles. APOE2 is associated with increased levels of APOE4 triglycerides and decreased levels of APOB and cholesterol.
11:45 APOEB is a lipoprotein found on the extracellular portion of VLDL remnant lipoproteins in LDL. It is involved in anthogenesis, causing the narrowing of the arteries.
12:09 APOE2 carriers tend to have a less atherogenic lipid profile.
12:15 APOE4 carriers are associated with decreased levels of APOE triglycerides and increased levels of APOB in lipoproteins
13:12 APOE4 puts genotype carriers at increased risk for heart disease. This is likely due to the association with APOE4 and elevated LDL and Apolipoprotein B.
14:07 APOE4 primes your microglia to be more inflammatory. Microglia are brain immune cells. They are involved in synaptic processing, pruning of cells, shaping neurons, and removing inflammatory debris. APOE4 carriers have decreased cerebral glucose metabolism and increased levels of beta amyloid and tau protein.
15:50 With APOE4, there are changes and increase of tau protein within the neurons. There are also alterations in the blood brain barrier integrity.
16:00 To preserve the integrity of the brain, moderate alcohol consumption, increase exercise, incorporate sauna therapy and sauna bathing, as it effects cerebral blood flow.
16:45 APOE is expressed in astrocytes, microglia and other vascular cells within the brain. Blood brain barrier prevents toxins and metabolic waste from going into your brain. Increased expression of APOE is detected in stressed neurons.
17:42 APOE isoforms affect lipid transport, glucose metabolism, mitochondrial function, synaptic plasticity, beta amyloid protein expression, tau protein and cerebral vascular function within the brain.
18:18 Ratio of APOE4 allele correlates with loss of gray matter volume and abnormal glucose metabolism, a hallmark of Alzheimer’s and dementia.
19:00 APOE4 is the greatest genetic risk factor for late onset Alzheimer’s disease. It also influences the risk and outcomes for stroke, MS, Parkinson’s disease, and frontotemporal dementia.
22:11 A low carb diet, high in wild caught fish, is protective for APOE4 carriers. It impacts brain metabolism and lipid levels favorably. Drive your glycemic load down.
24:05 If you are over the age of 50 and have one or two copies of the APOE4 allele, consider microdosing with rapamycin. Rapamycin is an mTOR inhibitor. It may delay the onset of Alzheimer’s and dementia.