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Alzheimer’s Disease Connection to Stroke Explained

March 22, 2008 By MedNews Leave a Comment

The risk of Alzheimer’s disease is nearly doubled among people who have had a stroke, and researchers at Columbia University Medical Center have found a process in the brain that explains the connection.

There is an increase in the production of the toxic amyloid beta (Aß) peptides after a stroke that are believed to cause Alzheimer’s disease. Results in this study showed that Aß production rises when there is an increase in production of a peptide called p25, which occurs in rodents and humans following a stroke. The Columbia team identified a pathway, known as p25/cdk5, whereby higher levels of p25 led to enhanced activity of a molecule called cdk5, which in turn led to a rise in the production of Aß

By reducing the activity of cdk5, by either an inhibitor or by genetic manipulation, lead author Karen found a decrease in Aß production in the brain, demonstrating that the p25/cdk5 pathway may be a treatment target for Alzheimer’s disease. Specifically, inhibitors of cdk5 are particular candidates for therapeutic development.

"This finding connects the dots between p25 and increased production of amyloid beta, and this p25/cdk5 pathway could explain why the risk of Alzheimer’s disease is significantly higher following a stroke," said Dr. Duff, professor of pathology (in psychiatry and in the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain) at Columbia University Medical Center and the New York State Psychiatric Institute. "However, we still need to verify that this pathway is actually set in motion after a stroke; right now the data is still circumstantial."

Dr. Duff’s laboratory is currently working on experiments to verify this pathway’s involvement using human post-mortem tissue of stroke patients. The specific pathway investigated was shown to be most active in young mice, as compared to older mice suggesting that p25/cdk5 may not be implicated in late-onset Alzheimer’s disease, the most common form of this neurodegenerative disease.

The research was published in the March 13, 2008 issue of Neuron.

Filed Under: Alzheimer's Tagged With: alzheimers, stroke



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