Isolation and characterization of apolipoproteins from murine microglia - Identification of a low density lipoprotein-like apolipoprotein J-rich but E-poor spherical particle

Amyloid A beta deposition is a neuropathologic hallmark of Alzheimer's disease. Activated microglia are intimately associated with plaques and appear to facilitate A beta deposition, an event believed to contribute to pathogenesis. It is unclear if microglia can modulate pathogenesis of Alzheimer's disease by secreting lipoprotein particles. Here we show that cultured BV2 murine microglial cells, like astrocytes, secrete apolipoprotein E (apoE) and apolipoprotein J (apoJ) in a time-dependent manner. To isolate and identify BV2 microglial particles, gel filtration chromatography was employed to fractionate BV2-conditioned medium. Analyses by Western blot, lipid determination, electron microscopy, and native gel electrophoresis demonstrate that BV2 microglial cells release spherical low density lipoprotein (LDL)-like lipid-containing particles rich in apoJ but poor in apoE, These microglial particles are dissimilar in size, shape, and lipoprotein composition to astrocyte-derived particles. The microglial-derived particles were tested for functional activity. Under conditions of suppressed de novo cholesterol synthesis, the LDL-like particles effectively rescued primary rat cortical neurons from mevastatin-induced neurotoxicity, The particles were also shown to bind A beta, We speculate that the LDL-like apoJ-rich apoE-poor microglial lipoproteins preferentially bind the lipoprotein receptor, recognizing apoJ, which is abundant in the choroid plexus, facilitating A beta clearance from the brain. BV2 cells also secrete an apoE-rich lipid-poor species that binds A beta. Consistent with the role of apoE in A beta fibril formation and deposition, this microglial species may promote plaque formation.