Apolipoprotein E (APOE) is a protein involved in the metabolism of fats in the body. It is implicated in Alzheimer’s disease and cardiovascular disease. APOE belongs to a family of fat-binding proteins called apolipoproteins. APOE interacts significantly with the low-density lipoprotein receptor (LDLR), which is essential for the normal processing (catabolism) of triglyceride-rich lipoproteins.
In peripheral tissues, APOE is primarily produced by the liver and macrophages, and mediates cholesterol metabolism. In the central nervous system, APOE is mainly produced by astrocytes and transports cholesterol to neurons via APOE receptors, which are members of the low density lipoprotein receptor gene family. APOE is the principal cholesterol carrier in the brain.
The ApoE gene provides instructions for making a protein called apolipoprotein E. In the brain, ApoE is involved in clearing harmful plaques that form around nerve cells. These plaques are a hallmark of Alzheimer’s disease and consist of damaged proteins called amyloid β which stick together to form the toxic plaques.
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. The E2 form is the most effective at removing Aβ plaque from the brain and subsequently is protective against Alzheimer’s disease. However, the E4 form of the ApoE protein is not very effective at removing Aβ plaque and carries an increased risk for developing Alzheimer’s disease.
ApoE combines with fats (lipids) in the body to form molecules called lipoproteins. Lipoproteins are responsible for packaging cholesterol and other fats and carrying them through the bloodstream. Maintaining normal levels of cholesterol is essential for the prevention of disorders that affect the heart and blood vessels (cardiovascular diseases), including heart attack and stroke. The ApoE test report includes results and comments related to both Cardiovascular and Alzheimer’s disease risk.
Ideal Candidates Have The Following Symptoms Or Conditions:
- Family history of dementia
- Symptoms of memory loss
- Pattern of decreasing intellectual ability
- Reduction in language and speech skills not related to other conditions
- NIH-funded research provides new clues on how ApoE4 affects Alzheimer’s risk. National Institutes of Health website.
https://www.nih.gov/news-events/news-releases/nih-funded-research-provides-new-clues-how-apoe4-affects-alzheimers-risk. Published May 16, 2012. Accessed December 4, 2019.
- Liu CC, Liu CC, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol. 2013;9(2):106-18.
- Shankar GM, Li S, Mehta TH, et al. Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nat Med. 2008;14(8):837-42.
- Prelli F, Castaño E, Glenner GG, Frangione B. Differences between vascular and plaque core amyloid in Alzheimer’s disease. J Neurochem. 1988;51(2):648-51.
- Strittmatter WJ, Saunders AM, Schmecheld et al. Apolipoprotein E: High-avidity binding to B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. PNAS. 1993:90;1977-1981.
- Aleshkov S, Abraham CR, and Zannis VI. Interaction of nascent ApoE2, ApoE3, and ApoE4 isoforms expressed in mammalian cells with amyloid peptide beta (1-40). Relevance to Alzheimer’s disease. Biochemistry. 1997:36(34);10571-80.
- Liu Y, Yu JT, Wang HF, et al. APOE genotype and neuroimaging markers of Alzheimer’s disease: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2015;86(2):127-34.
- Huang W, Qiu C, Von strauss E, Winblad B, Fratiglioni L. APOE genotype, family history of dementia, and Alzheimer disease risk: a 6-year follow-up study. Arch Neurol. 2004;61(12):1930-4.
- Weisgraber KH, Innerarity TL, Mahley RW. Abnormal lipoprotein receptor-binding activity of the human E apoprotein due to cysteine-arginine interchange at a single site. J Biol Chem. 1982;257(5):2518-21.
- Mahley RW, Huang Y, Rall SC. Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia). Questions, quandaries, and paradoxes. J Lipid Res. 1999;40(11):1933-49.
- Mahley RW, Rall SC. Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet. 2000;1:507-37.
- Mediterranean diet: A heart-healthy eating plan. Mayo Clinic website. https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthyeating/in-depth/mediterranean-diet/art-20047801. Accessed December 4, 2019.
- The Secret Behind the Mediterranean Diet. Life Extension website. https://www.lifeextension.com/magazine/2010/1/the-secret-behind-themediterranean- diet. Published January 2010. Accessed December 4, 2019.
- Nutrition and Healthy Eating. Mayo Clinic website. https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/indepth/nutrition-basics/hlv-20049477. Accessed December 4, 2019.
- Robinson JG, Stone NJ. Antiatherosclerotic and antithrombotic effects of omega-3 fatty acids. Am J Cardiol. 2006;98(4A):39i-49i.
- Thomas SR, Neuzil J, Mohr D, Stocker R. Coantioxidants make alpha-tocopherol an efficient antioxidant for low-density lipoprotein. Am J Clin Nutr. 1995;62(6 Suppl):1357S-1364S.
- Jie KG, Bots ML, Vermeer C, Witteman JC, Grobbee DE. Vitamin K status and bone mass in women with and without aortic atherosclerosis: a population-based study. Calcif Tissue Int. 1996;59(5):352-6.
- Geleijnse JM, Vermeer C, Grobbee DE, et al. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr. 2004;134(11):3100-519.
- Aviram M, Dornfeld L. Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure. Atherosclerosis. 2001;158(1):195-8.
- Aviram M, Rosenblat M, Gaitini D, et al. Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clin Nutr. 2004;23(3):423-33.
- Enhance Endothelial Health: How Pomegranate Protects Against Atherosclerosis. Life Extension website.
https://www.lifeextension.com/magazine/2014/11/enhance-endothelial-health-how-pomegranate-protects-against-atherosclerosis. Published November 2014. Accessed December 4, 2019.
- Hu S, Belcaro G, Cornelli U, et al. Effects of Pycnogenol® on endothelial dysfunction in borderline hypertensive, hyperlipidemic, and hyperglycemic individuals: the borderline study. Int Angiol. 2015;34(1):43-52.
- Belcaro G, Dugall M, Hosoi M, et al. Pycnogenol® and Centella Asiatica for asymptomatic atherosclerosis progression. Int Angiol. 2014;33(1):20-6.
- Cesarone MR, Belcaro G, Nicolaides AN, et al. Increase in echogenicity of echolucent carotid plaques after treatment with total triterpenic fraction of Centella asiatica: a prospective, placebo-controlled, randomized trial. Angiology. 2001;52 Suppl 2:S19-25.
- Akhtar MS, Ramzan A, Ali A, Ahmad M. Effect of Amla fruit (Emblica officinalis Gaertn.) on blood glucose and lipid profile of normal subjects and type 2 diabetic patients. Int J Food Sci Nutr. 2011;62(6):609-16.
- Cai F, Li C, Wu J, et al. Modulation of the oxidative stress and nuclear factor kappaB activation by theaflavin 3,3′-gallate in the rats exposed to cerebral ischemia-reperfusion. Folia Biol (Praha). 2007;53(5):164-72.
- Englisch W, Beckers C, Unkauf M, Ruepp M, Zinserling V. Efficacy of Artichoke dry extract in patients with hyperlipoproteinemia. Arzneimittelforschung. 2000;50(3):260-5.
- Rondanelli M, Giacosa A, Opizzi A, et al. Beneficial effects of artichoke leaf extract supplementation on increasing HDL-cholesterol in subjects with primary mild hypercholesterolaemia: a double-blind, randomized, placebo-controlled trial. Int J Food Sci Nutr. 2013;64(1):7-15.
- Rondanelli M, Castellazzi AM, Riva A, et al. Natural Killer Response and Lipo-Metabolic Profile in Adults with Low HDL-Cholesterol and Mild Hypercholesterolemia: Beneficial Effects of Artichoke Leaf Extract Supplementation. Evid Based Complement Alternat Med. 2019;2019:2069701.
- Evans M, Rumberger JA, Azumano I, Napolitano JJ, Citrolo D, Kamiya T. Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation. Vasc Health Risk Manag. 2014;10:89-100.
- Scarmeas N, Luchsinger JA, Schupf N, et al. Physical activity, diet, and risk of Alzheimer disease. JAMA. 2009;302(6):627-37.
- Larson EB, Wang L. Exercise, aging, and Alzheimer disease. Alzheimer Dis Assoc Disord. 2004;18(2):54-6.
- Hoffmann K, Sobol NA, Frederiksen KS, et al. Moderate-to-High Intensity Physical Exercise in Patients with Alzheimer’s Disease: A Randomized Controlled Trial. J Alzheimers Dis. 2016;50(2):443-53.
- How to Delay Brain Aging by 11 Years. Life Extension website. https://www.lifeextension.com/magazine/2016/4/how-to-delay-brain-aging-by-11-years. Published April 2016. Accessed December 5, 2019.
- Scarmeas N, Stern Y, Tang MX, Mayeux R, Luchsinger JA. Mediterranean diet and risk for Alzheimer’s disease. Ann Neurol. 2006;59(6):912-21.
- Yurko-mauro K, Mccarthy D, Rom D, et al. Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement. 2010;6(6):456-64.
- Yassine HN, Feng Q, Azizkhanian I, et al. Association of Serum Docosahexaenoic Acid With Cerebral Amyloidosis. JAMA Neurol. 2016;73(10):1208-1216.
- Yassine HN, Braskie MN, Mack WJ, et al. Association of Docosahexaenoic Acid Supplementation With Alzheimer Disease Stage in Apolipoprotein E ε4 Carriers: A Review. JAMA Neurol. 2017;74(3):339-347.
- Kato-kataoka A, Sakai M, Ebina R, Nonaka C, Asano T, Miyamori T. Soybean-derived phosphatidylserine improves memory function of the elderly Japanese subjects with memory complaints. J Clin Biochem Nutr. 2010;47(3):246-55.
- Schreiber S, Kampf-sherf O, Gorfine M, Kelly D, Oppenheim Y, Lerer B. An open trial of plant-source derived phosphatydilserine for treatment of age-related cognitive decline. Isr J Psychiatry Relat Sci. 2000;37(4):302-7.
- Szilágyi G, Nagy Z, Balkay L, et al. Effects of vinpocetine on the redistribution of cerebral blood flow and glucose metabolism in chronic ischemic stroke patients: a PET study. J Neurol Sci. 2005;229-230:275-84.
- Dézsi L, Kis-varga I, Nagy J, Komlódi Z, Kárpáti E. [Neuroprotective effects of vinpocetine in vivo and in vitro. Apovincaminic acid derivatives as potential therapeutic tools in ischemic stroke]. Acta Pharm Hung. 2002;72(2):84-91.
- Pereira C, Agostinho P, Oliveira CR. Vinpocetine attenuates the metabolic dysfunction induced by amyloid beta-peptides in PC12 cells. Free Radic Res. 2000;33(5):497-506.
- Mashayekh A, Pham DL, Yousem DM, Dizon M, Barker PB, Lin DD. Effects of Ginkgo biloba on cerebral blood flow assessed by quantitative MR perfusion imaging: a pilot study. Neuroradiology. 2011;53(3):185-91.
- Motoi Y, Shimada K, Ishiguro K, Hattori N. Lithium and autophagy. ACS Chem Neurosci. 2014;5(6):434-42.
- Nunes MA, Schöwe NM, Monteiro-silva KC, et al. Chronic Microdose Lithium Treatment Prevented Memory Loss and Neurohistopathological Changes in a Transgenic Mouse Model of Alzheimer’s Disease. PLoS ONE. 2015;10(11):e0142267.
- Nunes MA, Viel TA, Buck HS. Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer’s disease. Curr Alzheimer Res. 2013;10(1):104-7.
- Szaniszlo P, German P, Hajas G, Saenz DN, Kruzel M, Boldogh I. New insights into clinical trial for Colostrinin in Alzheimer’s disease. J Nutr Health Aging. 2009;13(3):235-41.
- Leszek J, Inglot AD, Janusz M, et al. Colostrinin proline-rich polypeptide complex from ovine colostrum–a long-term study of its efficacy in Alzheimer’s disease. Med Sci Monit. 2002;8(10):PI93-6.
- Slutsky I, Abumaria N, Wu LJ, et al. Enhancement of learning and memory by elevating brain magnesium. Neuron. 2010;65(2):165-77.
- Li W, Yu J, Liu Y, et al. Elevation of brain magnesium prevents synaptic loss and reverses cognitive deficits in Alzheimer’s disease mouse model. Mol Brain. 2014;7:65.
- Wang J, Liu Y, Zhou LJ, et al. Magnesium L-threonate prevents and restores memory deficits associated with neuropathic pain by inhibition of TNF-α. Pain Physician. 2013;16(5):E563-75.
- Zhang HY, Tang XC. Neuroprotective effects of huperzine A: new therapeutic targets for neurodegenerative disease. Trends Pharmacol Sci. 2006;27(12):619-25.
- Liang YQ, Tang XC. Comparative effects of huperzine A, donepezil and rivastigmine on cortical acetylcholine level and acetylcholinesterase activity in rats. Neurosci Lett. 2004;361(1-3):56-9.
- Li WM, Kan KK, Carlier PR, Pang YP, Han YF. East meets West in the search for Alzheimer’s therapeutics – novel dimeric inhibitors from tacrine and huperzine A. Curr Alzheimer Res. 2007;4(4):386-96.
- Kennedy DO, Pace S, et al. Effects of cholinesterase inhibiting sage (Salvia officinalis) on mood, anxiety and performance on a psychological stressor battery. Neuropsychopharmacology. 2006;31(4):845-52.
- Lopresti A et al. Salvia (Sage): A Review of its Potential Cognitive-Enhancing and Protective Effects. Drugs in R&D. 2017;17(1):53-64.
- Scholey AB, et al. An extract of Salvia (sage) with anticholinesterase properties improves memory and attention in healthy older volunteers. Psychopharmacology. 2008;198(1):127-39.