APOE + COMT: Cognitive function in aging

interactions between genes can tell us a lot

Hi there - 

This week's article is a quick one about a study that explored the interaction between the APOE gene (Alzheimer's risk factor) and COMT (neurotransmitter levels). The researchers looked at the way the different gene combinations, such as slow COMT and APOE E4, impacted memory and physical ability in people around age 70. 

The interaction between genetic variants is being studied more and more, and it is an important nuance to take into account when looking at your own genes. So I have a couple more quick articles in the works on gene X gene interactions. 

Gratefully yours, 

~ Debbie

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APOE and COMT: Cognitive performance in aging

For a long time, researchers focused on finding individual gene variants – SNPs – that were associated with traits or diseases. It was a one-to-one kind of relationship. Then came genome-wide association studies, which gave us multiple variants that had a tiny effect on a trait or disease. More recently, researchers have focused more on the interactions between polymorphisms with known, high-impact functional changes.

A new study of cognitive performance in aging looked at the interaction between two genes with known effects: APOE and COMT. [ref – open access study]

The APOE gene encodes a lipoprotein that plays a role in cholesterol transport and metabolism. Cholesterol is essential in the brain, and a variant in the APOE gene is one of the strongest common predictors of Alzheimer’s risk and cognitive impairment in aging. There are three common types of APOE, called E2, E3, and E4. Since you inherit one copy from each parent, you have six possible APOE types: E3/E3 (normal), E3/E4, E4/E4, E2/E3, and E2/E2 (rare). The E4 allele increases the risk of Alzheimer’s disease, with E4/E4 being associated with the highest rates of Alzheimer’s disease.

Related article: APOE and Alzheimer’s

The COMT gene codes for an enzyme that breaks down catecholamines, which is a class of molecules that includes several neurotransmitters. For example, COMT breaks down dopamine, and variants in the gene cause either slower or faster metabolism of dopamine.

Related article: COMT and Neurotransmitters

The COMT gene has a common variant called Val158Met or rs4680 that changes the stability of the enzyme. People with the low version of rs4680 (Met/Met) have about 40% lower COMT levels with reduced enzymatic activity compared to the Val/Val version.[ref]

COMT is thought to affect both cognition and motor function in aging through its effect on dopamine metabolism. Dopamine is important for memory and executive function, and it is also a critical component of motor function. For example, the loss of dopaminergic neurons causes the tremors and walking problems in Parkinson’s disease.

more....

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What I've been reading:

1. Optical stimulation of mitochondria reduces blood glucose levels 

This paper is still a pre-print, but it is a cool study. Essentially, the researchers showed that exposure to red light reduces maximum glucose spikes and decreases overall blood glucose response (27%!). The researchers exposed people with normal blood glucose response to 15 minutes of red light (670 nm) while doing a glucose tolerance test. Exposure to red light increases mitochondrial membrane potential and ATP production. In people with normal blood sugar response, this likely causes the mitochondria to use more glucose to create the ATP. 

While this is just a pre-print, I'm excited to see the study done in humans. Animal studies over the past few years have shown that exposure to red light reduces overall blood glucose and the spikes in blood glucose after eating sugar.[ref] 

My challenge to you this week - go outside (full sunlight) or find a red light source for 15 minutes after eating a meal. 

2. Prenatal exposure to common plasticizers: a longitudinal study on phthalates, brain volumetric measures, and IQ in youth
Phthalates are found in plastics and vinyls, but a big route of exposure is through artificial fragrances -- laundry detergents, air fresheners, and shampoos.

This study looked at phthalate levels in moms, and the researchers followed their kids for 14 years. The maternal phthalate concentrations in pregnancy correlated to brain volume in their kids at age 10 and lower IQ. The authors sum it up: " Our findings suggest the global impact of prenatal phthalate exposure on brain volumetric measures that extends into adolescence and underlies less optimal cognitive development. 

Related GL article: Detoxifying phthalates.