The Golgi complex plays an important role in cholesterol trafficking in cells, and amyloid ␤-peptides (A␤s) alter cholesterol trafficking. The hypothesis was tested that fresh and aged A␤-(1-42) would differentially modify Golgi cholesterol content in DINTC1 astrocytes and that the effects of A␤-(1-42) would be associated with the region of the Golgi complex. Two different methods were used to determine the effects of A␤-(1-42) on Golgi complex cholesterol. Confocal microscopy showed that fresh A␤-(1-42) significantly increased cholesterol and that aged A␤-(1-42) significantly reduced cholesterol content in the Golgi complex. Isolation of the Golgi complex into two fractions using density gradient centrifugation showed effects of aged A␤-(1-42) similar to those observed with confocal microscopy but revealed the novel finding that fresh A␤-(1-42) had opposite effects on the two Golgi fractions suggesting a specificity of A␤-(1-42) perturbation of the Golgi complex. Phosphatidylcholine-phospholipase D activity, cell membrane cholesterol, and apolipoprotein E levels were associated with effects of fresh A␤-(1-42) on cholesterol distribution but not with effects of aged A␤-(1-42), arguing against a common mechanism. Extracellular A␤-(1-42) targets the Golgi complex and disrupts cell cholesterol homeostasis, and this action of A␤-(1-42) could alter cell functions requiring optimal levels of cholesterol.

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