Terwel D, Steffensen KR, Verghese PB, Kummer MP, Gustafsson JÅ, Holtzman DM, Heneka MT.
Critical role of astroglial apolipoprotein E and liver X receptor-α expression for microglial Aβ phagocytosis.
J Neurosci. 2011 May 11;31(19):7049-59.
PubMed.
In this paper, Terwel et al. show that microglial uptake of fibrillar Aβ is reliant upon ApoE. They nicely show that this effect relies upon astrocytic liver X receptors (LXRs), consistent with the idea that LXR agonists act to elevate ApoE-containing HDL levels in the medium. An important finding is that this effect is LXRα dependent. This is significant since this isoform is inducible by PPARγ, and in humans is auto-induced.
One new observation is that LXR agonist treatment enhances microglia association with plaques in an LXRα-dependent manner, although the basis of this effect is unclear.
Overall, this paper adds new depth to the idea that LXRs and lipidated ApoE-containing HDLs play important roles in the normal clearance of fibrillar forms of amyloid, and that pharmacological targeting of LXRs is likely to be of therapeutic benefit.
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Indiana University School of Medicine
In this paper, Terwel et al. show that microglial uptake of fibrillar Aβ is reliant upon ApoE. They nicely show that this effect relies upon astrocytic liver X receptors (LXRs), consistent with the idea that LXR agonists act to elevate ApoE-containing HDL levels in the medium. An important finding is that this effect is LXRα dependent. This is significant since this isoform is inducible by PPARγ, and in humans is auto-induced.
One new observation is that LXR agonist treatment enhances microglia association with plaques in an LXRα-dependent manner, although the basis of this effect is unclear.
Overall, this paper adds new depth to the idea that LXRs and lipidated ApoE-containing HDLs play important roles in the normal clearance of fibrillar forms of amyloid, and that pharmacological targeting of LXRs is likely to be of therapeutic benefit.
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