A two-week course of high doses of CBD helped restore the function of two key proteins to reduce the accumulation of beta-amyloid plaque, a hallmark of Alzheimer’s disease, and improved cognition in an experimental family model of Alzheimer’s disease. early-onset, a form of Alzheimer’s disease that doctors know for sure is related to genes, the researchers report.
The proteins TREM2 and IL-33 are important for the ability of brain immune cells to literally consume dead cells and other debris such as beta-amyloid plaque that accumulates in the brain of patients, and levels of both decrease in the brain. Alzheimer’s.
Researchers report for the first time that CBD normalizes levels and function, improving cognition by more than sevenfold as it reduces levels of the immune protein IL-6 in mice, which is associated with the high levels of inflammation that are found in Alzheimer’s, says Dr. Babak Baban, an immunologist and associate dean of research at the Dental College of Georgia and corresponding author of the study.
He joined colleagues at the Medical College of Georgia, writing in the Alzheimer’s Disease Journal.
“Right now we have two classes of drugs to treat Alzheimer’s,” says Dr. John Morgan, a neurologist and director of the Movement and Memory Disorders Programs in the Department of Neurology at MCG. One class increases levels of the neurotransmitter acetylcholine, which is also decreased in Alzheimer’s, and another works through NMDA receptors involved in communication between neurons and important for memory.
“But we have nothing to affect the pathophysiology of the disease,” the co-author wrote.
Researchers at DCG and MCG decided to look at CBD’s ability to address some of the key brain systems that fail in Alzheimer’s disease.
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They found that CBD appears to normalize levels of IL-33, a protein whose highest expression in humans is normally found in the brain, where it helps to sound the alarm that there is an invader such as the accumulation of beta-amyloid. There is also emerging evidence for its role as a regulatory protein, whose role in increasing or decreasing the immune response depends on the environment, Baban says.
In Alzheimer’s disease, that includes reducing inflammation and trying to restore balance to the immune system. That up and down expression in health and disease could make IL-33 a good biomarker and treatment target for disease, the researchers say.
CBD also enhanced the expression of the activator receptor expressed on myeloid cells 2, or TREM2, which is found on the cell surface where it combines with another protein to transmit signals that activate cells, including immune cells. In the brain, its expression is found in microglial cells, a special population of immune cells found only in the brain, where they are key to eliminating invaders such as viruses and irrevocably damaged neurons.
Low levels of TREM2 and rare variations in TREM2 are associated with Alzheimer’s disease, and in their experiments with mice, supported by the National Institutes of Health, TREM2 and IL-33 were low.
Increase in useful proteins 7-10 times
They found that CBD treatment increased IL-33 and TREM2 levels seven times and ten times, respectively.
Both are essential for a natural and ongoing maintenance process in the brain called phagocytosis, in which microglial cells regularly consume amyloid beta, which is regularly produced in the brain, as a result of the breakdown of the amyloid beta precursor protein, which is important for the synapses, or connection points, between neurons, and that the plate disrupts.
The impact of CBD on brain function in the early-onset Alzheimer’s mouse model was evaluated using methods such as the ability to differentiate between a familiar and a new element, as well as observation of the movement of rodents.
People with Alzheimer’s can experience movement problems like stiffness and gait disturbance, says Dr. Hesam Khodadadi, a graduate student working in Baban’s lab. Mice with the disease run in an endless closed circle, behavior that was halted with CBD treatment, says Khodadadi, the study’s first author.
The next steps include determining optimal dosages and administering CBD earlier in the disease process. The compound was administered in the later stages of the published study and now researchers are using it at the first signs of cognitive decline, Khodadadi says. They are also exploring delivery systems, including the use of an inhaler that should help deliver CBD more directly to the brain. For published studies, CBD was placed in the belly of the mice every other day for two weeks.
One company has developed inhalers for both animals and humans for researchers who have also been exploring the effect of CBD on adult respiratory distress syndrome, or ARDS, a build-up of fluid in the lungs that is a major and deadly complication of COVID-19, as well as other serious illnesses like sepsis and severe trauma. The doses of CBD used for the Alzheimer’s disease study were the same that the researchers successfully used to reduce the “cytokine storm” of ARDS, which can irrevocably damage the lungs.
Familial disease is an inherited version of Alzheimer’s disease in which symptoms usually appear in the 30s and 40s and occurs in approximately 10-15% of patients.
CBD should be at least as effective in the more common, unfamiliar type of Alzheimer’s that likely has more targets for CBD, Baban notes. They are already analyzing its potential in a more common model of this type and moving forward to establish a clinical trial.
Plaques and neurofibrillary tangles, a collection of the protein tau within neurons, are the main components of Alzheimer’s, Morgan says. Beta-amyloid usually appears in the brain 15 to 20 years or more before dementia, he says, and the appearance of tau tangles, which can occur up to 10 years later, correlates with the appearance of dementia. There is some interaction between beta amyloid and tau that decrease each other’s dysfunction, Morgan notes.
The Food and Drug Administration is scheduled to issue a ruling in early June on a new drug, aducanumab, that would be the first to attack and help eliminate beta amyloid, Morgan says.
(Source: Augusta University Media)
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