Genetic Clues to a Happy, Health Brain

The health of the brain is dependent on numerous things; environment, lifestyle and genetics. Many people can see how they are likely to age by observing changes in their parents, and fears can often grow concerning the genetics of aging. Aside from rare genetic conditions like early onset Alzheimer’s Disease, there are several more common genetic polymorphisms that play an important role in brain health. Genes like APOE, NOS3/eNOS, FUT2, and MTHFR can play important roles in the amount of blood flow, nutrient content, and plaque formation in the brain.

The NOS3/eNOS gene encodes for an enzyme that is responsible for maintaining baseline vascular nitric oxide (NO)1. Nitric oxide is responsible for vasodilation, or the relaxation of vascular smooth muscle cells allowing greater blood flow and reduced blood pressure2. Individuals with risk alleles for this gene have been shown to have increased risk for developing hypertension as well as late onset Alzheimer’s disease.3 Uncontrolled hypertension in midlife can contribute an increased risk of developing dementia later in life.4

Two other genes that can contribute to the increased risk of developing late onset Alzheimer’s disease in an aging population are MTHFR and APOE.5-6 These genes encode for products that are important not only for cardiovascular health but for the health of the brain. Risk alleles in the MTHFR gene have been shown to increase homocysteine levels which are important for cardiovascular health.7 The APOE gene encodes for a protein whose role is to transport cholesterol throughout the body and clear plaques from the brain. These important proteins play a critical role in the protection of the brain from factors that increase the damage associated with aging.

Another important gene that can affect the health of the brain is the FUT2 gene. Certain genotypes at this gene locus have been shown in studies to affect serum levels of B12.8 In a study conducted by a research team out of Oxford University it was found that patients who maintained a higher serum B12 level were six times less likely to experience brain shrinkage compared with those who had lower levels of the vitamin in their blood.9 FUT2 and MTHFR also work together to maintain brain health through the creation of SAMe which, in turn, maintains the methylation reactions whose inhibition is considered to cause cobalamin deficiency associated neuropathy.10

There are many factors that play a role in brain health; environment, lifestyle, and genetics. Increasing research in the area of SNPs and the detection of risk alleles have shown a correlation between increased risk for developing late onset of dementia and Alzheimer’s disease. Being able to detect this increased risk as well as understanding the exact biochemistry involved in decreased brain function can be invaluable to increasing health.


1. Marsden PA et al. Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem. 1992; 68:17478-17488.
2. Cosentino F and Luscher TF. Maintenance of vascular integrity: role of nitric oxide and other bradykinin mediators. Eur Heart J. 1995; 16 Suppl K:4-12.
3. Xie X et al. Endothelial nitric oxide synthase gene single nucleotide polymorphisms and the risk of hypertension: A meta-analysis involving 63,258 subjects. Clinical and Experimental Hypertension. 2017; 39(2):175-182.
4. Kennelly S et al. Blood Pressure and Dementia- A Comprehensive Review. Ther Adv Neurol Disord. 2009 Jul; 2(4): 241–260.
5. Hua Y et al. Association between the MTHFR gene and Alzheimer’s disease: a meta-analysis. Int J Neurosci. 2011 Aug;121(8):462-71. doi: 10.3109/00207454.2011.578778. Epub 2011 Jun 10.
6. Lambert J et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nature Genetics volume 45, pages 1452–1458 (2013).
7. Refsum H et al. The Hordaland Homocysteine Study: A Community-Based Study of Homocysteine, Its Determinants, and Associations with Disease. J Nutr. 2006; 136:1731S-1740S.
8. Hazra A et al. Common variants of FUT2 are associated with plasma vitamin B12 levels. Nat. Genet. 2008; 40:1160–1162.
9. Vogiatzoglou A et al. Vitamin B12 status and rate of brain volume loss in community-dwelling elderly. Neurology. 2008 Sep 9;71(11):826-32. doi: 10.1212/01.wnl.0000325581.26991.f2.
10. Weir D et al. Brain function in the elderly: role of vitamin B12 and folate. Br Med Bull. 1999;55(3):669-82.