SAN FRANCISCO, CA January 5, 2008 Scientists from the Gladstone Institute of Neurological Disease (GIND), UCSF, and Stanford have discovered that a certain type of collagen, collagen VI, protects brain cells against amyloid-beta (Aβ) proteins, which are widely thought to cause Alzheimer's disease (AD). While the functions of collagens in cartilage and muscle are well established, before this study it was unknown that collagen VI is made by neurons in the brain and that it can fulfill important neuroprotective functions.
The team of investigators led by GIND director Lennart Mucke, MD, reported in the current edition of the journal Nature Neuroscience, that collagen VI is increased in brain tissues of Alzheimer's patients.
"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.
The Gladstone team had profiled changes in gene expression using DNA microarrays, which provides an unbiased method for identifying key biological pathways. By comparing all of the genes that are active in disease and normal tissue, one can get valuable information on new pathways and potential therapeutic targets.
The researchers looked at the dentate gyrus, a specific area of the brain that is critical to memory and particularly vulnerable in AD, and compared the genes that were turned on and off in normal mice and a mouse model of AD. This analysis revealed the striking increase in collagen VI in the brains of mice that model AD.
Building on this initial finding, the team 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 neurons, the very cells that the disease attacks and that we all need to think and remember. <
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