Recently scientists from the Gladstone Institute of Neurological Disease (GIND), UCSF, and Stanford have discovered that a certain type of collagen protects your brain from the deadly proteins associated with forgetfulness.
Most people are aware of how important collagen is for your joint cartilage and muscle tissue, but prior to this study no one knew just how important it was to your brain.
In fact, prior to this study it was unknown that this particular type of collagen known as collagen VI is actually made by neurons in the brain.
Or that it can fulfill important neuroprotective functions.
But that’s exactly what was reported by a team of investigators, led by GIND director Lennart Mucke, MD, in a recent edition of the journal Nature Neuroscience.
What they found is that collagen VI is increased in brain tissues of patients forgetfulness.
"We first noticed the increase in collagen VI in the brain of AD mouse models, which inspired us to look for it in the human condition and to define its role in the disease," said Dr. Mucke.
By comparing all of the genes that are active in both diseased and normal tissue, they were able to uncover valuable information on new pathways and potential therapeutic targets.
The researchers looked at a specific area of the brain called the dentate gyrus.
This area is known to be critical to memory and particularly vulnerable in AD.
Researchers compared the genes that were turned on and off in normal mice versus a mouse model of AD.
This analysis revealed the striking increase in collagen VI in the brains of mice that model AD.
Based off these findings the team then examined brain tissue from AD patients and normal non-demented humans and found that collagen VI expression was also higher in the AD patients.
They further discovered that the cellular source of the collagen VI in the brain was the neurons themselves.
In fact, the very cells that the disease attacks!
"These findings were really surprising and exciting to us because nobody knew anything about collagen VI in the brain," said Jason Cheng, MD, co-lead author of the study. "We were particularly curious whether collagen VI contributed to neuronal damage in AD or was produced as a defense mechanism against it," added Dena Dubal, MD, PhD, co-lead author of the study.
To answer these questions, the scientists net carried out a series of informative cell culture experiments.
These experiments revealed found that when the proteins associated with forgetfulness were added to neurons grown in culture it increased the expression of collagen VI.
They also discovered that increasing the amount of collagen VI in the cultures effectively protected the neurons against toxicity.
"This striking protective effect suggests that increased neuronal production of collagen VI is an important component of the brain's defense against Aβ," said Dr. Mucke. "It made us really curious about the underlying mechanisms."
Dr. Mucke's team took it one step further and examined the direct interactions of collagen VI with the forgetfulness proteins.
They looked at how the forgetfulness protein attacks individual neurons in cell culture.
Normally small poisonous assemblies of these proteins, called oligomers, bind strongly to vulnerable neurons in the brain, but in the presence of collagen VI, this binding was blocked.
Using specialized imaging they showed that collagen VI and the forgetfulness proteins form large aggregates with each other that may keep the smaller, more toxic protein complexes away from neurons.
"We are eager to explore how this kind of process might be enhanced therapeutically and how we can best leverage it for the development of more effective treatments for this devastating condition," said Dr. Dubal.