Soc for Neuroscience Annual Meeting: Lipoproteins Reduce Clearance of Aβ
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Using exquisite human primary cortical cultures containing neurons, astrocytes, and microglia, Nadeau (319.1) demonstrated that addition of VLDLs or HDLs increased media levels of both Aβ40 and Aβ42. Moreover, addition of ApoE3, Apo4 or ApoA1 caused elevations in Aβ similar to that induced by HDL, whereas other plaque associated proteins such as C1q had no effect. To determine if the increase was due to altered production he examined FLAPP and APP CTFs and found no effect. He then added 35S-labeled cell-derived Aβ back to unlabeled cortical cultures and found that addition of HDL prevented clearance of Aβ. Interestingly, addition of insulin at concentrations less than or equal to 10 micromolar also reduced Aβ degradation, leading Nadeau to speculate that IDE (also see 122.11) was the principal Aβ degrading activity in these cultures and that Aβ could escape IDE-mediated degradation by binding to lipoproteins.
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