Alcohol flush has an effect on Alzheimer's Disease risk?

Ever sipped a beer and felt your face flare up like a firecracker? That’s an alcohol flush reaction; a genetic quirk that’s more than a party embarrassment. It’s tied to the ALDH2 gene, and a recent study published by Nature Communications has even linked this gene to amyloid beta buildup in the brain, a phenomenon heavily correlated to Alzheimer's Disease. But before you get too worried, let's take a quick look at the details.  

Asian Flush: A Window into Your Genes and Amyloid Beta

The alcohol flush reaction occurs when your body struggles to process alcohol. Normally, your liver converts alcohol into acetaldehyde, a toxic byproduct, and then into other harmless substances which are passed out of the body. The enzyme behind that second step? Aldehyde dehydrogenase 2 (ALDH2).

For some, a genetic variant rs671 makes ALDH2 about as useful as a broken umbrella in a rainstorm. This variant is found in 30-50% of people in countries like China, Japan, and Korea, hence the flush’s nickname “Asian Glow”.

These faulty enzymes lead to accumulation of harmful byproducts in your body, one of those being 4-HNE, a molecule that can damage brain cells and increase the production of amyloid beta protein, which could potentially wreak havoc.

How Asian Flush Fuels Amyloid Beta Buildup 

Amyloid beta proteins are like sticky notes gone rogue in your brain. They can clump together into plaques that disrupt brain cell communication, a key feature of Alzheimer’s disease. A Nature Communications study examined 469 postmortem brains and found that those with the ALDH2 rs671 variant—the same variant causing Asian Flush—had:

• More amyloid beta plaques: Brains with the variant were loaded with these sticky protein clumps compared to those without.

• Higher amyloid beta 40/42 ratio: The variant boosts production of amyloid beta 40 over amyloid beta 42, tipping the scales toward more plaque formation.

The variant’s weak enzyme lets 4-HNE accumulate, which in turn supercharges the production of amyloid beta 40 in brain cells, making plaques more likely to form. Plus, the variant hampers the brain’s ability to clear amyloid beta and control inflammation, amplifying existing problems, with a 20-30% higher amyloid beta 40/42 ratio in brains with the rs671 variant . The same genetic glitch that makes your face glow red after a drink also sets the stage for amyloid beta to wreak havoc in your brain, but there is no significant evidence showing that this variant directly causes Alzheimer's Disease.   

Amyloid Beta and Alzheimer’s: The Bigger Picture 

On the other hand, amyloid beta’s role in Alzheimer’s is well-documented. These plaques are a hallmark of the disease, contributing to memory loss and cognitive decline. The amyloid beta 42/40 ratio is a crucial diagnostic marker for Alzheimer’s, with a higher proportion of amyloid beta 40often correlating with worse disease progression. Furthermore, amyloid beta plaques can appear years preceding Alzheimer’s symptoms, making them a critical target for early intervention.

What’s Next? Your Genes, Your Power   

If you experience Asian Flush, you might carry the rs671 variant, meaning your brain could be more susceptible to amyloid beta plaques, which could in turn lead to other disorders.

 But here’s the silver lining: a genetic test can prevent any worries, giving you a clear picture of your brain health to catch potential issues early. Genetic testing is your best tool to stay ahead of the curve, and a simple test can help with timely diagnoses and crucial monitoring, empowering you to make the choices necessary to protect your health.

 

Keep up to learn more genetic fun facts with Codex!

References:

- Wang, X., et al. (2024). The aldehyde dehydrogenase 2 rs671 variant enhances amyloid β pathology. Nature Communications, 15, 2594. https://doi.org/10.1038/s41467-024-46899-0 

- Hansson, O., et al. (2019). Advantages and disadvantages of the use of the CSF Amyloid β (Aβ) 42/40 ratio in the diagnosis of Alzheimer’s Disease. Alzheimer’s Research & Therapy, 11, 34. https://doi.org/10.1186/s13195-019-0485-0 

- Gomez-Isla, T., & Frosch, M. P. (2022). Lesions without symptoms: understanding resilience to Alzheimer disease neuropathological changes. Nature Reviews Neurology, 18, 323-332. https://doi.org/10.1038/s41582-022-00652-9