Widespread distribution of phospholipid transfer protein (PLTP) in human central nervous system: evidence for PLTP synthesis by glia and neurons and for increased levels in Alzheimer's disease

Simona Vuletic, Lee-Way Jin, Santica M. Marcovina, Elaine R. Peskind, Thomas Möller, and John J. Albers

Medicine, University of Washington, Seattle, Washington 98103

Corresponding Author: jja{at}u.washington.edu

Plasma phospholipid transfer protein (PLTP) is one of the key proteins in lipid and lipoprotein metabolism. We examined PLTP distribution in human brain, using PLTP mRNA dot-blot, Northern blot, immunohistochemistry, Western blot and phospholipid transfer activity assay analyses. PLTP mRNA of 1.8 kb was widely distributed in all the examined regions of the central nervous system at either comparable or slightly lower levels than in the other major organs, depending on the region. Cerebrospinal fluid phospholipid transfer activity represented 15% of the plasma activity, indicating active PLTP synthesis in the brain. Western blot and phosholipid transfer activity assay demonstrated secretion of active PLTP by neurons, microglia and astrocytes in culture. Immunohistochemistry demonstrated PLTP presence in neurons, astrocytes, microglia and oligodendroglia. Some neuronal groups, such as nucleus hypoglossus and CA2 neurons in hippocampus, ependymal layer and choroid plexus were particularly strongly stained, with substantial glial and neuropil immunostaining throughout the brain. Comparison between brain tissues from patients with Alzheimer’s disease (AD) and non-AD subjects revealed significant increase (p=0.02) in PLTP levels in brain tissue homogenates and increased PLTP immunostaining in AD.

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