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Alzheimer Clue: Link Between ApoE And Amyloid Found

Date:
March 12, 1999
Source:
Washington University School Of Medicine
Summary:
Researchers have discovered that a blood protein called apoE slows the deposition of amyloid-beta peptide in the brain. This peptide forms the sticky plaques that dot the brains of Alzheimer patients.

St. Louis, March 10, 1999 — Researchers have discovered that a blood protein called apoE slows the deposition of amyloid-beta peptide in the brain. This peptide forms the sticky plaques that dot the brains of Alzheimer patients.

"This is the first experiment that clearly demonstrates that human apoE affects amyloid-beta metabolism in vivo," says David M. Holtzman, M.D., assistant professor of neurology and molecular biology & pharmacology at Washington University School of Medicine in St. Louis.

The researchers report their findings in the March 15 issue of the Journal of Clinical Investigation (JCI). The lead authors are Holtzman and scientists Kelly R. Bales and Steven Paul of Lilly Research Laboratories in Indianapolis.

ApoE is found in the lipid-protein complexes that move lipids around the body, and the most common form is apoE3. In 1993, scientists discovered that people with a version called apoE4 are at risk for developing Alzheimer’s disease at an earlier age than people with apoE3 or apoE2. They speculated that apoE and amyloid-beta peptide might interact, though this was not clear.

Holtzman inserted the gene for human apoE into mice that were unable to make their own apoE. Then he and his colleagues at Lilly crossbred these animals with mice that made human amyloid-beta peptide.

The latter develop amyloid plaques in the brain by 9 months of age. But the mice that also made human apoE3 or human apoE4 had no amyloid plaques by that time. "At this early time point, human apoE is somehow enhancing amyloid clearance and/or decreasing fibril formation," Holtzman says. The amyloid in plaques takes the form of fibrils.

This finding was surprising because the Lilly researchers previously had found that mice with the human amyloid gene deposit less amyloid-beta peptide when their apoE gene is missing.

In the JCI paper, the researchers suggest that human apoE particles might somehow remove amyloid out of incipient plaques the way it removes cholesterol out of atherosclerotic plaques in arteries. "This suggests the intriguing possibility that raising levels of apoE might slow the onset or progression of Alzheimer’s disease," Holtzman says.

It is possible that apoE4 is a risk factor for Alzheimer’s because it does not prevent amyloid deposition as efficiently as apoE3 rather than because it somehow damages brain cells. To find out if this could be the case, the researchers are extending their studies of the apoE3 and apoE4 mice, which eventually do deposit amyloid.

**************************************

Grants from the National Institute on Aging, the Alzheimer’s Association, the Ruth K. Broad Foundation and a Paul Beeson Scholar Award from the American Federation for Aging Research supported this research.

Holtzman DM, Bales KR, Wu S, Bhat P, Parsadanian M, Fagan AM, Chang LK, Sun Y, Paul SM. Expression of human apolipoprotein E reduces amyloid- deposition in a mouse model of Alzheimer’s disease. Journal of Clinical Investigation, vol. 103, pp. R15 to R20.

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. "Alzheimer Clue: Link Between ApoE And Amyloid Found." ScienceDaily. ScienceDaily, 12 March 1999. <www.sciencedaily.com/releases/1999/03/990312062057.htm>.
Washington University School Of Medicine. (1999, March 12). Alzheimer Clue: Link Between ApoE And Amyloid Found. ScienceDaily. Retrieved September 17, 2014 from www.sciencedaily.com/releases/1999/03/990312062057.htm
Washington University School Of Medicine. "Alzheimer Clue: Link Between ApoE And Amyloid Found." ScienceDaily. www.sciencedaily.com/releases/1999/03/990312062057.htm (accessed September 17, 2014).

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