Asian Flush's Connection to Alzheimer's

Joshi, A. U., Van Wassenhove, L. D., Logas, K. R., Minhas, P. S., Andreasson, K. I., Weinberg, K. I., Chen, C. H., & Mochly-Rosen, D. (2019). Aldehyde dehydrogenase 2 activity and aldehydic load contribute to neuroinflammation and Alzheimer's disease related pathology. Acta neuropathologica communications, 7(1), 190. https://doi.org/10.1186/s40478-019-0839-7

Alzheimer’s disease (AD) is a leading neurodegenerative disorder and the most common form of dementia, affecting approximately 55 million people globally. Unfortunately, recent analyses have shown that this number will increase, with the World Alzheimer Report of 2018 predicting 150 million cases by 2050. The increase in cases is largely a result of an aging population, as the neural cells within the brain aren’t able to divide. This is important as cell division allows for tissue to renew itself, so the neuron’s inability to divide will result in a build-up of toxic molecules within the cell. The most common examples of these compounds are amyloid-beta (Aβ) peptides and tau proteins, both cited as a key cause of Alzheimer’s. More specifically, Aβ peptides increase the rate of damage to fat molecules, resulting in the buildup of toxic organic compounds like aldehydes.

Alcohol is the 3rd highest risk factor in developed countries, associated with high blood pressure, stroke, and digestive problems. When alcohol gets converted into energy, it releases a chemical called acetaldehyde that can cause heart cancer. Additionally, alcohol has been attributed to the prognosis of dementia as it causes an increase in Aβ peptides within neurons. An enzyme that is responsible for breaking down the toxins of acetaldehyde is called ALDH2. In approximately 560 million East Asians, the ALDH2 enzyme has a genetic error that causes it to malfunction and prevents the breakdown of acetaldehyde. In fact, this error results in the phenomenon known as “Asian flush”: when East Asians drink alcohol and experience redness on their face.

In order to examine a potential link between ALDH2 and Alzheimer’s, a group of researchers used various strains of mice and analyzed various chemical properties within their neurons. They found that less expression of ALDH2 caused defects in the mitochondria, a cell organelle that is responsible for the production of energy. In addition, the ALDH2 mutation caused significant brain damage coupled with tau protein accumulation. Reactive oxygen species (ROS), a group of reactive molecules that help create energy, began to increase in concentration within the mouse brain, resulting in mitochondrial death and neurodegeneration. When measuring cell count, the scientists found that a lack of ALDH2 expression caused brain tissue necrosis, or death, as well as cell death. When examining the effect of alcohol consumption, they saw that the brain became increasingly sensitive to alcohol with greater ingestion, triggering mitochondrial dysfunction and a further buildup of ROS. There was also a loss of synapse function, the connection between two neurons for information sharing.

Based on their results, the researchers concluded that chronic alcohol consumption and ALDH2 mutations may contribute to mitochondrial dysfunction and immune system reactions within neurons, potentially increasing the risk of AD. Previous studies suggest a connection between ALDH2 mutations and late-onset AD, or the development of AD at age 65 or older, particularly when combined with the other genetic forms of AD.

Though the gene mutation may appear to be frightening, it is important to note that AD is multifaceted and influenced by various genetic and lifestyle factors. Alcohol consumption and ALDH2 represent only one part of AD.

By Brenton

Works Cited:

Alzheimer’s disease: Facts & figures. BrightFocus. (n.d.). https://www.brightfocus.org/alzheimers/article/alzheimers-disease-facts-figures#:~:text=Alzheimer’s%20is%20on%20the%20rise,Alzheimer’s%20disease%20or%20other%20dementias.

Centers for Disease Control and Prevention. (2022, April 14). Drinking too much alcohol can harm your health. learn the facts. Centers for Disease Control and Prevention. https://www.cdc.gov/alcohol/fact-sheets/alcohol-use.htm