Alzheimer clue would this also be true with CJD?

[Guest guest]

Alzheimer Clue: Link Between ApoE And

Amyloid Found

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 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

R. Bales and 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 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, SM. Expression of human

apolipoprotein E reduces

amyloid-ß 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

-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 -Jewish and St. Louis

Children's hospitals, the School

of Medicine is linked to BJC Health System.

Editor's Note: The original news release can be found

at

http://medicine.wustl.edu/~wumpa/news/holtz2.html