Consider this analogy: the brain is a factory. Our workforce, which consists of over 100 billion neurons, connect together to form various groups, all of which have special jobs. These jobs include tasks connected to physical sensations, like breathing and seeing, along with more abstract processes, like cognition, learning, and memory. In order for these networks to operate smoothly, they must receive supplies, create energy, form equipment, remove waste, store information, and communicate with other cells. Coordination is key to keeping the factory running.

Diseases such as Alzheimer’s, however, interrupt these intricate interactions. Although the origin is still unclear, scientists believe that the disease is responsible for backups and breakdowns, which eventually spiral and cause problems in other regions (Alzheimer’s Association, 2019). Eventually, the factory loses its ability to function, and irreversible damage is done. In real life, this may present as confusion, difficulty with logical thinking, inability to learn new things, and increased memory loss.

So, what factors may play into the development of Alzheimer’s? Well, for years, researchers have focused on two proteins: amyloid beta and tau. It was noted that abnormal tau accumulates in brain areas involved in memory, and beta-amyloid clumps and builds up between neurons; as beta-amyloid levels reach a certain point, tau rapidly spreads throughout the brain, demonstrating a complex interaction that feeds into itself (National Institute on Aging, 2017). As the combination of the proteins is a key indicator of the disease, scientists hypothesized that decreasing levels would improve symptoms. Experimental trials failed to show any real improvements in memory or affective behaviors, however, and in one case, removal of amyloid actually seemed to make patients worse (Weintraub, 2019). So, back to square one. What were they missing?

More recent findings point to a new mechanism that may be involved with the progression of Alzheimer’s: inflammation, or more specifically, neuroinflammation. Neuroinflammation–the inflammation that takes place in the central nervous system–is characterized by over-activation of neuroglial cells and expression of major pro-inflammatory cytokines (Andy et al., 2018). These cytokines, which are chemicals of the immune response, are associated with an abundance of negative outcomes, including anxiety, depression, autoimmune disorders, heart problems, and more. Neuroglial cells–immune cells of the central nervous system which are normally meant to remove waste and debris–are suggested to excessively amass in the brains of those with Alzheimer’s, contributing to the inflammation and failing to complete their normal toxin-clearing duties (National Institute on Aging, 2017). According to Paul Morgan, a professor of immunology at Cardiff University, “The accumulating evidence that inflammation is a driver of this disease is enormous. It makes very good biological sense,” (Weintraub, 2019).

This explanation would account for a phenomenon that has stumped past Alzheimer’s research: some people with “amyloid plaques” and “tau tangles” still think and behave normally (Weintraub, 2019). According to neurologists, these patients may be able to resist the negative effects of the proteins due to a lack of neuroinflammation; their resilient immune systems are able to withstand the early infections that set off the amyloid and tau positive feedback loop and subsequent neurodegeneration.

What does this mean about future treatments? Well, these findings suggest that one way to reduce symptoms may be to target inflammation. One rat study found that administration of the compound deoxyelephantopin (DET) ameliorated such neuroinflammation in subjects by reducing activation of the responsible neuroglial cells, thereby suppressing pro-inflammatory regulators, decreasing production of pro-inflammatory cytokines, and increasing production of anti-inflammatory chemicals (Andy et al., 2018). Consequently, the cognitive impairments associated with this over-activation, swelling, and eventual death of cells was also attenuated; these promising treatments have been shown to reverse behavioral and memory deficits, and lessen the expression of Alzheimer’s markers. Although it is too soon to say for sure, DET may possibly be developed as a therapeutic agent moving forward for neurodegenerative disorder patients who have previously been unresponsive to treatments.

References

Andy, S. N., Pandy, V., Alias, Z., & Kadir, H. A. (2018). Deoxyelephantopin ameliorates lipopolysaccharides (LPS)-induced memory impairments in rats: Evidence for its anti-neuroinflammatory properties. Life sciences, 206, 45-60.

Alzheimer’s Association. (2019). What Is Alzheimer’s? Retrieved from https://www.alz.org/alzheimers-dementia/what-is-alzheimers

National Institute on Aging. (2017, May 16). What Are the Signs of Alzheimer’s Disease? Retrieved from https://www.nia.nih.gov/health/what-are-signs-alzheimers-disease

Weintraub, K. (2019, March 04). For Alzheimer’s Sufferers, Brain Inflammation Ignites a Neuron-Killing “Forest Fire”. Retrieved from https://www.scientificamerican.com/article/for-alzheimers-sufferers-brain-inflammation-ignites-a-neuron-killing-forest-fire/