A study team may have discovered a new technique to eliminate toxic proteins in the brain that drive cognitive disorders such as Alzheimer’s and Parkinson’s, paving the way for new treatments for the debilitating conditions.
Experts believe that Alzheimer’s disease is caused by amyloid beta proteins accumulating and aggregating in the brain, causing symptoms such as memory loss and decline in general cognitive function.
The Washington University School of Medicine in St. Louis, Missouri, discovered that increasing amounts of a different protein, aquaporin 4, could aid in their removal.
In a study on mice designed to produce more amyloid beta, those given chemicals that increased the levels of aquaporin 4 removed the dangerous proteins more quickly than those given a placebo or inert liquid.
Each year, around 500,000 Americans are diagnosed with Alzheimer’s, and 120,000 succumb to the disease. The study indicates that a higher level of aquaporin 4 may help prevent the disease, but may not cure it. However, it is unclear what causes Alzheimer’s disease, and some experts believe that a buildup of amyloid beta is not always to blame.
In the study, which was published on Wednesday in the journal Brain, researchers first examined how aquaporin 4 is produced in the brain.
Occasionally, this protein is produced with what they refer to as a ‘little tail’ at the end.
Initially, the scientists believed this to be a fluke due to an error in the protein production process.
However, studies swiftly discovered that the DNA coding for this alteration existed in numerous species.
In addition, astrocytes, which govern the flow of water and nutrients into the brain from the blood, were shown to be normally present.
They theorized that its “tail end” served as a blood artery flap to regulate the exchange of water and nutrients. They hypothesized that the more aquaporin 4 and the more frequently it opened and closed the flap, the more amyloid beta would be flushed from the brain.
To test the hypothesis, scientists increased aquaporin 4 levels in mice genetically modified to produce more amyloid beta.
Dr. Darshan Sapkota, the study’s leading scientist, evaluated 2,560 chemicals to see which would be able to increase production.
Apigenin, generally found in chamomile, parsley, onions, and other plants, and sulphaquinoxaline, an antibiotic used by veterinarians, were the two he chose to explore.
In the trial, mice were divided into five or six groups and administered apigenin, sulphaquinoxaline, a harmless liquid, and a placebo.
Each mouse had a needle inserted into its brain that was connected to a machine that delivered the chemical being studied for around 20 hours.
Those who received the chemicals eliminated amyloid beta faster than those who did not.
The levels of amyloid beta were measured every hour, but Dr. John Cirrito, a neuroscientist at Washington University, reported that a difference between the two groups became apparent within hours of the beginning of the experiment.
Cirrito said, in response to a question about whether the results indicated that people should hurry to purchase chamomile, onions, and other plants with high apigenin levels, No, we are not yet there.
The data indicate that something truly special is occurring here. We know that it affects amyloid beta, but the likelihood is that it will also affect others.’
Apigenin is available as a dietary supplement, but he cautioned against taking excessive doses because its effects are unknown.
It is unsafe for humans to swallow the antibiotic sulphaquinoxaline, which is generally used to treat illnesses in cattle and sheep.
To continue their research, scientists are currently searching for more chemicals that could be utilized to reduce brain amyloid beta molecules. A non-needle method of delivering the chemicals to the brain is also being studied.
They suggest that human trials could be conducted within a decade of further research.
However, scientists are uncertain as to what causes Alzheimer’s disease, which affects over six million Americans.
The accumulation of amyloid beta in the brain is the prevalent theory because the plaques disrupt cell communication. However, some research suggests that although this is connected with the illness, it may not be the primary reason.
A study conducted by the University of California, San Diego, and published in 2020 on 700 individuals is among many that imply amyloid beta may be connected with the illness in some situations rather than the underlying cause.
Dr. Cirrito continued, ‘Numerous studies indicate that decreasing amyloid levels by just 20 to 25 percent prevent amyloid accumulation, at least in mice, and our results were similar.
This suggests that this could be a novel treatment for Alzheimer’s disease and other neurodegenerative illnesses involving protein aggregation in the brain.
There is no evidence that this process is exclusive to amyloid beta. It may also be boosting alpha-synuclein clearance, which could assist Parkinson’s disease patients.’
Examining sulphaquinoxaline and other chemicals, the team is currently attempting to identify medications that would alter the production of aquaporin 4 to develop therapeutics.
Sapkota continued, ‘We are seeking something that can be rapidly implemented in the clinic.
Simply knowing that it can be targeted by medicine is a good indicator that there will be something out there that we can use.
National Institute of Neurological Disorders and Strokes provided partial funding for the study.
Sapkota directed the research as a post-doctoral fellow at Washington University; he is now an assistant professor of biological sciences at the University of Texas at Dallas.
Alzheimer’s disease is the most prevalent form of dementia, affecting around six million Americans at present.
It is believed to be caused by the aberrant accumulation of proteins, notably amyloid beta, in and around brain cells. Other participants are known as tau.
Scientists are uncertain as to why these substances accumulate in some individuals, but it may be related to hereditary factors, food, or a brain injury, among other things.
