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Scientists Link apoE To A Major Cause Of Bleeding Strokes

Date:
June 6, 2000
Source:
Washington University School Of Medicine
Summary:
Researchers have discovered a direct link between a protein called apoE and cerebral amyloid angiopathy (CAA), which causes up to one-third of bleeding strokes in the elderly. Mice that were unable to make apoE did not line blood vessels of the brain with amyloid deposits that, in humans, damage vessel walls, allowing blood to leak into brain tissue.

Researchers have discovered a direct link between a protein called apoE and cerebral amyloid angiopathy (CAA), which causes up to one-third of bleeding strokes in the elderly. Mice that were unable to make apoE did not line blood vessels of the brain with amyloid deposits that, in humans, damage vessel walls, allowing blood to leak into brain tissue.

"Our study demonstrates that apoE is required for the buildup of an abnormal protein called amyloid in the walls of brain blood vessels. So decreasing the expression of apoE might inhibit this buildup of amyloid and therefore lower the risk for cerebral hemorrhage," says David M. Holtzman, M.D.

Holtzman is lead author of a paper in the June 1 issue of Annals of Neurology that describes this finding. He is an associate professor of neurology and of molecular biology and pharmacology at Washington University School of Medicine in St. Louis.

Holtzman previously showed that apoE promotes the conversion of amyloid-beta peptide, the protein fragment associated with Alzheimer's disease, into hair-like fibrils that damage brain cells. In the current study, he confirmed that conclusion. But he also studied the deposition of amyloid-beta peptide on the walls of the brain's blood vessels.

The mice in the study contained a human gene discovered in a Swedish family of Alzheimer patients. It makes the animals deposit amyloid-beta peptide on brain tissue, mimicking a key feature of Alzheimer's disease. But Holtzman and his collaborators showed that these mice also deposit the peptide in blood vessel walls in certain parts of the brain by 12 months of age. So the animals also display the key feature of CAA.

When the researchers analyzed mice that contained the human Alzheimer gene but whose apoE genes had been inactivated, they found no deposits of beta-amyloid peptide in the brain's blood vessels.

They also treated sections of mouse brains with stains that react only with the toxic, fibrillar form of amyloid-beta peptide. They detected the fibrillar peptide in the mice that could make apoE but not in those that could not.

"Our study shows that apoE plays an essential role in depositing amyloid-beta peptide in the brain's blood vessels," Holtzman says. "The direct implication is that it also is required to damage blood vessels due to amyloid-beta buildup. So apoE might be a good target for preventing this pathology. Decreasing its expression or preventing it from interacting with amyloid-beta peptide potentially would prevent the occurrence of CAA."

Holtzman's team now is studying the cerebrovascular effects of the different forms of apoE, which occurs in humans as apoE2, apoE3 or apoE4. People with CAA are about twice as likely to have the gene for apoE4 than the general population, suggesting that this form might create more damage to the brain's blood vessels than the more common form, apoE3. ApoE4 already is known to be a risk factor for Alzheimer's disease.

Holtzman DM, Fagan AM, Mackey B, Tenkova T, Sartorius L, Paul SM, Bales K, Ashe KH, Irizarry MC, Hyman BT. Apolipoprotein E facilitates neuritic and vascular plaque formation in an Alzheimer's disease model. Annals of Neurology, June 1, 2000.

Holtman also is a member of the Center for the Study of Nervous System Injury and the Alzheimer's Disease Research Center at Washington University School of Medicine in St. Louis. This study was funded by the National Institute on Aging, the Monsanto/Searle Washington University Biomedical Research Program, the Ruth K. Broad Foundation and the American Federation for Aging Research.

The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC Health System.


Story Source:

The above story is based on materials provided by Washington University School Of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

Washington University School Of Medicine. "Scientists Link apoE To A Major Cause Of Bleeding Strokes." ScienceDaily. ScienceDaily, 6 June 2000. <www.sciencedaily.com/releases/2000/06/000602073447.htm>.
Washington University School Of Medicine. (2000, June 6). Scientists Link apoE To A Major Cause Of Bleeding Strokes. ScienceDaily. Retrieved September 19, 2014 from www.sciencedaily.com/releases/2000/06/000602073447.htm
Washington University School Of Medicine. "Scientists Link apoE To A Major Cause Of Bleeding Strokes." ScienceDaily. www.sciencedaily.com/releases/2000/06/000602073447.htm (accessed September 19, 2014).

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