Some studies have suggested that alcohol consumption could expose people to a heightened risk of developing Alzheimer's disease later in life. But the mechanics behind this relationship have been unclear — until now.
In the brain, Alzheimer's is characterized by the formation of beta-amyloid plaques.
These sticky clumps of the amyloid beta protein interfere with signals transmitted between brain cells, therefore obstructing the circulation of information in the brain.
However, the mechanisms involved in rendering the brain more vulnerable to this condition have largely remained unclear.
And though this may offer some clues as to the pathways through which alcohol may predispose a person to the development of Alzheimer's disease, the existing research had not shown which of the genes affected by alcohol consumption would normally protect the brain against neurodegeneration.
Recently, specialists from the University of Illinois at Chicago took steps to more clearly identify the pathways through which heavy alcohol use can impair the protective mechanisms that shield the brain against neuronal damage.
Their results, showing how alcohol can stop the brain from clearing out amyloid beta (which is the protein that forms obstructive clusters in Alzheimer's) are now published in the Journal of Neuroinflammation.
Gene expression altered by alcohol
Lead author Dr. Douglas Feinstein and colleagues used rat microglial cells — immune cells found in the brain and the spinal chord — to identify which genes would be affected both by exposure to alcohol and by high levels of inflammation in said cells.
The reason they chose to work with microglial cells specifically is because these cells are normally "tasked" with
This process is known as "phagocytosis," which roughly translates as "the action of cells eating."
At the same time, microglial cells are known to
Taking this into account, the researchers experimented with microglial cells from rats by exposing them to alcohol, cytokines (substances that help to boost the inflammatory response), or both alcohol and cytokines.
The exposure lasted, in each case, 24 hours, after which point Dr. Feinstein and team investigated any changes that had occurred in gene expression as a result of each of these experiments.
Also, the researchers scrutinized the effect that alcohol had on microglia's ability to clear amyloid beta.
They found that 312 genes presented altered expression following exposure to alcohol only, while the same was true for 3,082 genes after cytokine-only exposure, and 3,552 genes following concomitant exposure to both cytokines and alcohol.
An average of 16 percent of genes showed alterations in their expression levels, which ranged from a 50 percent decrease in expression compared with normal levels to a 72 percent increase in expression compared with the norm.
Alcohol aids accumulation of harmful protein
That being said, only very few genes played a role in both the phagocytosis of amyloid beta and inflammatory processes at cellular level.
"Among the genes we saw altered were many involved in phagocytosis," says Dr. Feinstein, "which is the first time this has been shown."
"While these studies were performed in isolated cells," he goes on to explain, "our results suggest that alcohol impedes the ability of microglia to keep the brain clear of amyloid beta and may contribute to the development of Alzheimer's disease."
Importantly, when the team tried exposing the microglia to alcohol levels consistent with those that might be seen in humans who binge drink — or who have a heavy drinking habit — they saw that the microglial cells' ability to clear amyloid beta was suppressed by approximately 15 percent following only 1 hour of exposure.
This led the researchers to conclude that it may be impaired microglial phagocytosis due to the effect of alcohol that could leave the brain vulnerable to neurodegeneration.
"We didn't continue the study to see whether phagocytosis was further impaired after longer exposures to alcohol, but it appears that these changes in microglial cells could be a contributing factor to the development of Alzheimer's disease."
Dr. Douglas Feinstein