Posted on Oct 13, 2020, 5 p.m.
Binge drinking may be linked to the onset and severity of Alzheimer’s disease, and it might strike younger and in a more severe form, scientists are embarking on a path to try and decipher the molecular steps involved in how excessive alcohol consumption leads to the most common form of dementia.
Scientists from Feinstein Institutes for Medical Research are building on the premise of excessive alcohol consumption being toxic to the brain; binge drinking likely plays an insidious part in the alteration of a normal brain protein into a biological rogue that is highly prevalent in Alzheimer’s disease: TAU.
Tau can be found in its normal confirmation in neurons modulating the stability of axonal microtubules, but in its abnormal conformation has long been considered to be one of the leading hallmarks of the disease and it makes up the tangles in the notorious plaques and tangles pathology. Plaques are the deposits of the protein beta-amyloid, this research however involves binge drinking and Alzheimer’s dementia and tau.
The team believes that they are on the potential breakthrough path in the investigation to have a definitive explanation of how tau transforms from a normal protein into a neuron annihilating cause of the disease under the influence of excessive alcohol intake. They are already studying how tau can become phosphorylated, meaning how its structural conformation changes and its role in the brain becomes chemically altered under the influence of binge drinking.
"Studies have shown that frequent and heavy alcohol drinking is linked to earlier onset and increased severity of Alzheimer's disease," Dr. Max Brenner, assistant professor at the Feinstein Institutes told Medical Xpress. "It has been reported that alcohol consumption correlates with Alzheimer's-like cortical atrophy in individuals at high risk of developing the disease as well as younger age of onset. In addition, chronic alcohol exposure caused neural tau phosphorylation in the hippocampus and memory-impairment in Alzheimer's-predisposed mice," Brenner said.
The goal is to identify specific proteins that play key roles in the proliferation of tau, and to understand the activities of cold-inducible RNA-binding proteins and its associated form, extracellular cold-inducible RNA-binding protein.
"CIRP is normally present in the cell nucleus where it helps to regulate which proteins each cell produces," Brenner explained. "When cells detect potentially harmful conditions, such as alcohol exposure, they release molecules like eCIRP to alert other cells nearby to start preparing their defenses to overcome the stress conditions. The cells being alerted recognize eCIRP outside the cell when it binds to specific protein receptors in the cell membrane. The cascade of eCIRP proteins is triggered when alcohol diffuses throughout the brain, and while alcohol is a major influence, the eCIRP cascade can occur under other deleterious conditions. A number of potentially harmful conditions trigger the release of eCIRP, including low oxygen, low temperature and radiation exposure," Brenner said.
This debilitating brain-wasting disease is the 6th leading cause of death in America, and it is the most common form of neurodegenerative dementia. Alzheimer’s disease afflicts some 5.8 million people across the nation, and around the globe, this disease is inexorably increasing with an estimated 50 million people believed to be living with this disease as well as other forms of dementia. The number of affected people is projected to reach 152 million on a global scale according to the United Nations unless therapeutics are discovered that can stop the continuously escalating number of cases. The team is theorizing that blocking eCIRP may prove to be a viable treatment for alcohol-related AD.
In addition to contributing to AD, binge drinking is also a major societal and public health concern. In America, the CDC has found an array of common collateral problems that are associated with the addictive habit: falls, burns, alcohol poisoning and car crashes; domestic violence, homicide, and intimate partner violence, sexual assault, sexually transmitted disease and suicides have also been traced back to binge drinking. Additionally, roughly half of all alcohol-related deaths within America are directly related to binge drinking.
Binge drinkers can have a blood alcohol concentration ranging anywhere from 0.08% to substantially higher, according to the team. Although their research is providing clues, thus far the team is uncertain about the precise sequence of mechanisms that are involved in how excessive alcohol consumption leads to the disease. But they are aware that eCIRP is a key mediator of memory impairment induced by exposure to binge drinking levels of alcohol.
"Early-stage studies suggest that alcohol aggravates beta-amyloid deposition by increasing the levels of amyloid precursor protein (APP), which increases the enzyme that changes the precursor into beta-amyloid and decreases the cellular disposal of beta-amyloid. We have decided to focus our research on the effects of alcohol on tau, however, because tau deposition correlates better with the cognitive decline in Alzheimer's disease than beta-amyloid," Brenner said.
The National Institutes of Health have awarded the team a $419,000 grant to further investigate the roles of alcohol in the development of the disease.
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