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Columbia recognizes pathway between Alzheimer’s and stroke PDF Print E-mail
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by William Atkins   
Sunday, 20 April 2008
Researchers at the Columbia University Medical Center indicated on March 13, 2008 that they have discovered a molecular pathway in the brain that links Alzheimer’s disease and stroke.


Published in the March 13, 2008 issue of the journal Neuron, the study discovered a molecular pathway in the brain that involves the production of a protein, which is thought to increase its production of amyloid beta (ab) peptides after strokes have occurred.

These ab peptides, a peptide of 39-43 amino acids, is the main constitutent of amyloid plaques in the brains of Alzheimer's patients. They are thought to cause Alzheimer’s disease.

Within rodents and post-mortem tissue in humans, the researchers found that after a stroke occurred a pathway (called p25/cdk5) produced higher levels of a peptide (called p25) that caused increased activity of a molecule (called cdk5) that led to more production of ab peptides—which, as stated earlier, is thought to cause Alzheimer’s disease.

Lead author and U.S. pathologist Karen Duff—a 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—and her fellow colleagues specifically reduced the activity of the molecule cdk5.

By doing so, either by introducing an inhibitor or by genetic manipulation, they found that the production of ab peptides decreased. Their results indicate that the p25/cdk5 pathway may be a possible treatment for Alzheimer’s disease.

Duff explains, “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. However, we still need to verify that this pathway is actually set in motion after a stroke; right now the data is still circumstantial.” [Columbia University Medical Center: “Research illuminates link between Alzheimer’s and stroke”]

Thus, Duff’s Columbia laboratory is now working on further experiments to verify this pathway’s involvement using human post-mortem tissue of stroke patients.

The Neuron article is called “Transcriptional Regulation of β-Secretase by p25/cdk5 Leads to Enhanced Amyloidogenic Processing.”

Duff’s collaborators in the study are Yi Wen, W. Haung Yu, Bryan Maloney, Jason Bailey, Junrong Ma, Isabelle Marié, Thomas Maurin, Lili Wang, Helen Figueroa, Mathieu Herman, Pavan Krishnamurthy, Li Liu, Emmanuel Planel, Lit-Fui Lau, and Debomoy K. Lahiri.

The educational facilities of the researchers include: Taub Institute at Columbia University Medical Center (New York City); Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine (Indianapolis); Department of Pathology, New York University School of Medicine (New York City); and CNS Discovery, Pfizer Global Research and Development (Groton, Connecticut).

More about Duff's paper and Alzheimer's disease on the next page.



 
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