Astrocytes may play an active role in degrading amyloid-β (Aβ), the peptide found in the amyloid plaques that clog the intracellular space in the brains of people with Alzheimer's disease, according to a paper in the March 3 Nature Medicine online.
Astrocytes are one of the major cell groups found in the central nervous system and are often thought of as housekeeping cells that roam the CNS, maintaining a healthy environment for neurons. Now, principal author Jens Huseman of Columbia University, New York, together with colleagues in California, show that astrocytes can track down and destroy amyloid plaques.
First author Tony Wyss-Coray, Stanford University, tested the ability of adult astrocytes to migrate toward a source of monocyte chemoattractant protein -1 (MCP-1), a molecule found in amyloid plaques and previously shown to cause migration of neonatal astrocytes. When Wyss-Coray and colleagues used MCP-1 to coax adult astrocytes across a collagen membrane, twice as many cells migrated as when MCP-1 was absent. Furthermore, when the authors loaded the membrane with Aβ1-42, the most amyloidogenic form of the peptide, not only did astrocytes stop at the membrane, but they also engulfed the Aβ. This finding prompted the authors to expose cultured astrocytes to the peptide; within three hours the Aβ had been taken up by the cells, and by 48 hours had vanished from both the culture medium and the astrocytes.
The authors conclude that their observations might explain why astrocytes are commonly found gathering at Aβ hotspots in AD brains. They also suggest that astrocyte activity around AD plaques may be beneficial, a suggestion that has been debated for some time (see Wyss-Coray and Mucke, 2002).—Tom Fagan
- Wyss-Coray T, Mucke L. Inflammation in neurodegenerative disease--a double-edged sword. Neuron. 2002 Aug 1;35(3):419-32. PubMed.
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- Wyss-Coray T, Loike JD, Brionne TC, Lu E, Anankov R, Yan F, Silverstein SC, Husemann J. Adult mouse astrocytes degrade amyloid-beta in vitro and in situ. Nat Med. 2003 Apr;9(4):453-7. PubMed.