Heart Health, Brain Health and Apolipoprotein E.

The heart and the brain may seem separate at first glance, but doctors know everything is connected. Heart and brain health are important to help patients to both survive, and thrive. One of the key players in the health of these two systems is a protein by the name of Apolipoprotein E (ApoE). ApoE is an important lipid transporting protein whose job is to carry cholesterol from the blood into the cell; it is the principle cholesterol carrier of the brain.1 The gene that encodes for ApoE can produce three different isoforms of the protein depending of which allele is carried. These different isoforms can affect the body differently causing either an increase or decrease in both cardiovascular health as well as plaque formation in the brain.2 So what are the three isoforms of ApoE and how do they affect patients?

The three isoforms: ApoE2, ApoE3, and ApoE42 have different effects on the body. Of the three, ApoE3 is considered the wild type; it neither increases nor decreases the chance of developing cardiovascular disease or Alzheimer’s disease.2 People with this isoform transport cholesterol into cells at a normal rate. However people with the isoform E4 have difficulty with cholesterol transportation which causes a buildup of cholesterol in the vascular system which leads to atherosclerosis.3 Another way in which the Apoe4 isoform can affect the body is by reduced break down of peptide beta amyloid plaques (Aβ) which are seen to be high in patients with Alzheimer’s disease.4-6 Lastly the isoform E2 actually conveys a decreased chance of developing cardiovascular disease and has been shown to increase the breakdown of Aβ plaques in the neural tissue causing a protective effect to the brain.7 However in less than 2% of people with the E2/E2 genotype a condition can develop called type III hyperlipoproteinemia which is characterized by high levels of total cholesterol, LDL and triglycerides. People who have two copies of the E2/E2 allele will benefit greatly from routine lab work checking their cholesterol and triglyceride levels.2,7

Apolipoprotein E may seem like one tiny little player in the lipid transport pathway, but its variation in isoforms can have serious effects on a patient. Prior knowledge of a person’s genotype can be a huge advantage to managing their care. When a patient presents with a family history of either Alzheimer’s Disease or Cardiovascular Disease, it is worth testing the gene to understand the particular risk that patient is facing. Information confers power, knowing the risk can help both you and the patient take proactive steps to maintain health for as long as possible.


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  2. Weisgrabert K., InnerarityT., Mahley R. Abnormal Lipoprotein Receptor-binding Activity of the Human E Apoprotein due to Cysteine-Arginine Interchange at a Single Site. March 10, 1982 Journal of Biological Chemistry. Vol 257. Pp. 2518-2521
  3. Mahley, Robert, Rall SC Apolipoprotein E:far more than a lipid transport protein. Annual Rev Genomics Hum Genet. 200; 1:507-37.
  4. Liu CCI, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol. 2013 Feb 9 (2):106-18. Doi: 10.1038/nrneurol. 2012.263.
  5. Liu Y1, Yu JT2, Wang HF3, Han PR4, Tan CC5, Wang C5, Meng XF5, Risacher SL6, Saykin Aj6, Tan L2. APOE genotype and neuroimaging markers of
  6. Alzheimer’s disease: systematic review and meta-analysis. Neurol Neurosurg Psychiatry. 2015 Feb;86(2):127-34. Doi: 10.1136/jnnp-2014-307719.
  7. Haung Wl, Qiu C, von Strauss E, Winblad B, Fratiglioni L. APOE genotype, family history of dementia, and Alzheimer’s disease risk: a 6-year follow-up study. Arch Neurol. 2004 Dec; 61 (12):1930-4.
  8. Mahley, Robert, Hauang, Yadong, Rall C. Stanley Jr. Pathogenesis of type III hyperlipoproteinemia (dsybetalipoporteinemia): questions, quandaries and paradoxes. Journal of Lipid Research. 1999. 40:1933-1949.