Collagen VI may help protect the brain against Alzheimer... (/p These findings were really surpri...)

Collagen VI may help protect the brain against Alzheimer's disease

Date:1/5/2009

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"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 this and other questions, the scientists carried out a series of informative cell culture experiments. These experiments revealed found that Aβ added to neurons grown in culture increased the expression of collagen VI and that this process involved the immune regulatory cytokine TGFβ. What is more, the team discovered that increasing the amount of collagen VI in the cultures effectively protected the neurons against Aβ 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."

To clinch these mechanisms, Dr. Mucke's team examined the direct interactions of collagen VI with Aβ. They looked at how Aβ attacks individual neurons in cell culture. Small poisonous Aβ assemblies, called oligomers, bind strongly to vulnerable neurons in the brain, but in the presence of collagen VI, this binding was blocked. Using immunohistochemistry and atomic force microscopy, they showed that collagen VI and Aβ form large aggregates with each other that may sequester the smaller, more toxic Aβ 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.

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Contact: Valerie Tucker
vtucker@gladstone.ucsf.edu
415-734-2019
Gladstone Institutes
Source:Eurekalert

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