Sci. Aging Knowl. Environ., 5 March 2003
Astrocytes melt amyloid plaques
R. John Davenporthttp://sageke.sciencemag.org/cgi/content/full/sageke;2003/9/nw39
Key Words: phagocyte amyloid precursor protein
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 -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 -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 -amyloid protein, the astrocytes stuck. The results suggest that plaques lure astrocytes with enticing proteins, and then the cells clasp amyloid. The investigators next tested whether astrocytes, like microglia, could dissolve amyloid plaques. They covered a glass surface with 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, amyloid first accumulated inside the astrocytes and subsequently disappeared, suggesting that the cells dissolve plaques by absorbing the protein gunk and then destroying it.
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 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 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
March 5, 2003
Science of Aging Knowledge Environment. ISSN 1539-6150