CBD improves cognition in Alzheimer’s model

High doses of cannabidiol restores protein function to reduce beta-amyloid plaques in Alzheimer’s.

Alzheimer’s disease is a neurodegenerative disease that causes beta-amyloid plaques to build up in the brain, a key distinction for those who suffer from this type of dementia. An experimental model of early onset familial Alzheimer’s by the Dental College of Georgia at Augusta University demonstrates that a two-week course of high doses of CBD (cannabidiol, which is derived directly from the hemp or cannabis plant), can restore the function and levels of two crucial plaque-removing proteins, TREM2 and IL-33.

Longevity.Technology: CBD oil is wearing two hats at the moment, being hailed as an investigative new drug by some, while still a regular and beneficial supplement for others. The FDA urges caution, making it clear that it has “seen only limited data about CBD safety [1]“, but its ability to address some of the key brain pathways mean that further research, both in terms of CBD’s potential and ensuring its safety are needed. There is a very real need to improve outcomes for Alzheimer’s sufferers, and this study, albeit murine, is cause for cautious optimism.

The study found that CBD appears to normalise levels of IL-33; this protein is mostly expressed in the brain, where it signals the presences of invaders, such as beta amyloid build-up. In addition, research points to IL-33 having a regulatory role as well [2], as it can dial immune response either up or down as the environment dictates. In Alzheimer’s, that means it can turn down inflammation and help restore balance to the immune system.

The research team felt that IL-33’s up and down expression could warrant IL-33’s consideration as both a clear biomarker and a treatment target for disease [3].
Proteins TREM2 and IL-33 play a key role in the continual housekeeping that occurs in the brain; microglial cells engulf dead cells and beta amyloid in a process called phagocytosis.

Alzheimer’s sufferers can experience movement problems such as shuffling, stiffness, drifting to the side or an impaired gait; mice with Alzheimer’s run in an endless tight circles, but this behaviour was arrested when the mice were treated with CBD.

Beta amyloid is produced in the brain when amyloid-beta precursor proteins degrade. Amyloid-beta precursor proteins are concentrated in the synapses of neurons, functioning as cell surface receptors and playing a part in synapse formation and neural plasticity. As they degrade, the microglial cells should clear these by-products away, but if this process doesn’t happen, in part due to a lack of key ‘helper’ proteins TREM2 and IL-33, the beta amyloid forms clumps of plaque, which cause toxic damage to nerve cells and interrupt normal brain function.

By restoring the function and levels of these proteins, cognition and function in the mice model was shown to improve in the study. Brain function in the mice was assessed by methods like the ability to differentiate between familiar and new items and the rodents’ movement. The study found that CBD treatment effectively increased IL-33 levels sevenfold, and TREM2 tenfold [4].

Alzheimer’s sufferers can experience movement problems such as shuffling, stiffness, drifting to the side or an impaired gait; mice with Alzheimer’s run in an endless tight circles, but this behaviour was arrested when the mice were treated with CBD.

CBD also reduce levels of the immune protein IL-6, which is associated with the high inflammation levels found in Alzheimer’s disease.

“Right now we have two classes of drugs to treat Alzheimer’s,” says Dr John Morgan, neurologist and director of the Movement and Memory Disorder Programs in the MCG Department of Neurology and study co-author. “One class increases levels of the neurotransmitter acetylcholine, which also are decreased in Alzheimer’s, and another works through the NMDA receptors involved in communication between neurons and important to memory. But we have nothing that gets to the pathophysiology of the disease [3].”

Familial Alzheimer’s is an inherited version of the disease; symptoms typically manifest in the patient’s 30s or 40s and it accounts for about 10-15% of patients, and like the more typical late-onset Alzheimer’s, the familial version is incurable [5].

The researchers hope CBD should be at least equally effective in the more common version of Alzheimer’s, and are already are planning a model for this, with a view to moving towards establishing a clinical trial.

[1] https://bit.ly/3lSVeUK
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255965/
[3] https://jagwire.augusta.edu/cbd-reduces-plaque-improves-cognition-in-model-of-familial-alzheimers/
[4] https://content.iospress.com/articles/journal-of-alzheimers-disease/jad210026
[5] https://www.alzforum.org/early-onset-familial-ad/overview/what-early-onset-familial-alzheimer-disease-efad

Image credit: The Dental College of Georgia, left to right; Babak Baban, John Morgan and Hasan Khodadadi

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