From SAGE KE - Science of Aging
Knowledge Environment

Clearance Cell: Astrocytes melt amyloid
plaques


A trash-collecting cell might clean the
brain, according to new work. Cells called
astrocytes dissolve amyloid plaques that
characterize Alzheimer's disease (AD),
researchers report. The study is the first
to hint that astrocytes incinerate the
protein conglomerates and suggests that
goading the cells might slow progression
of the brain-ravaging disease.

Clumps of b-amyloid protein pervade the
brains of patients with AD (see
"Detangling Alzheimer's Disease"), and
the junk attracts the body's attention. For
instance, cells called microglia, which
remove molecular debris that arises from
brain injury and disease, shatter plaques
coated with antibodies. Other brain cells
known as astrocytes--which help regulate
ion concentrations and adjust neuron
firing--also accumulate around b-amyloid
deposits, but scientists haven't known
what the cells do.

To decipher their function, Jens
Husemann, an immunologist at
Columbia University in New York City, and
colleagues purified astrocytes from adult
mice and examined their behavior in
culture. The researchers placed cells on
one side of a porous membrane and put
a cell-attracting protein found in amyloid
plaques on the other side. As expected,
the astrocytes slithered through the
membrane toward the protein. But when
the researchers coated the membrane
with b-amyloid protein, the astrocytes
stuck. The results suggest that plaques
lure astrocytes with enticing proteins, and
then the cells clasp b amyloid. The
investigators next tested whether
astrocytes, like microglia, could dissolve
amyloid plaques. They covered a glass
surface with b amyloid linked to a
fluorescent molecule and added
astrocytes. After 2 days, the cells had
cleared an amyloid-free ring around
themselves on the plate. Over the course
of the experiment, b amyloid first
accumulated inside the astrocytes and
subsequently disappeared, suggesting
that the cells dissolve plaques by
absorbing the protein gunk and then
destroying it.



Like a cheap suit. Astrocytes (green)
glom onto aggregates of b-amyloid
protein (red). [Credit: T.
Wyss-Coray/Stanford University]

The researchers next tested whether
astrocytes could disintegrate plaques in
brain tissue. They prepared sections of
hippocampus--a region responsible for
learning and memory where amyloid
plaques appear in AD--and added
astrocytes. After 2 days, the
astrocyte-treated tissue contained half as
much b amyloid as did untreated brain
slices. Together, the results suggest that
astrocytes flock to amyloid deposits and
munch them up. Further work is needed
to clarify how astrocytes function in living
brains, says Husemann.

The study reveals "a whole new cell type
to try and manipulate with drugs" to
combat AD, says neurologist Samuel
Gandy of Thomas Jefferson University in
Philadelphia. Because astrocytes don't
seem to require antibodies to attack b
amyloid, activating the cells might
circumvent the side effects of an
experimental AD vaccine that showed
promise in mice but caused dangerous
brain swelling in people. Astrocytes also
churn out the ApoE protein, certain
versions of which increase susceptibility
to AD, says geneticist Ralph Martins of
the University of Western Australia in
Perth. He would like to know whether
mutations in ApoE hinder astrocytes from
vaporizing amyloid plaques, which could
explain why such genetic changes
increase the likelihood of AD. Identifying
the molecules that enable astrocytes to
clean up amyloid might reveal ways to
prod these trash removers to work
overtime.

--R. John Davenport; suggested by Amir
Sadighi Akha

T. Wyss-Coray et al., Adult mouse
astrocytes degrade amyloid-b in vitro and
in situ. Nat. Med., 3 March 2003 [e-pub
ahead of print]. [Abstract/Full Text]