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Originally published In Press as doi:10.1194/jlr.M300046-JLR200 on April 1, 2003

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Journal of Lipid Research, Vol. 44, 1113-1123, June 2003
Copyright © 2003 by Lipid Research, Inc.

Widespread distribution of PLTP in human CNS

: evidence for PLTP synthesis by glia and neurons, and increased levels in Alzheimer's disease

Simona Vuletic*, Lee-Way Jin{dagger}, Santica M. Marcovina1,*, Elaine R. Peskind**,{dagger}{dagger}, Thomas Möller§ and John J. Albers2,*,{dagger}

* Department of Medicine, University of Washington, Seattle, WA 98195
{dagger} Northwest Lipid Research Laboratories, Department of Pathology, University of Washington, Seattle, WA 98195
§ Department of Neurology, University of Washington, Seattle, WA 98195
** School of Medicine, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA 98195
{dagger}{dagger} Mental Illness Research, Education, and Clinical Center, Veteran's Administration Puget Sound Health Care System, Seattle, WA 98108

2 To whom correspondence should be addressed. e-mail: 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 (IHC), 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. IHC 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 nonAD subjects revealed a significant increase (P = 0.02) in PLTP levels in brain tissue homogenates and increased PLTP immunostaining in AD.

Abbreviations: ABC, avidin biotin complex; AD, Alzheimer's disease; CNS, central nervous system; CSF, cerebrospinal fluid; DAB, 3,3'-diaminobenzidine; FFPE, formalin-fixed, paraffin-embedded; GFAP, glial fibrillary acidic protein; HRP, horseradish peroxidase; IHC, immunohistochemistry; MAb, monoclonal antibody; MBP, myelin basic protein; PLTA, phospholipid transfer protein activity; PLTP, phospholipid transfer protein

Supplementary key words brain tissue • cerebrospinal fluid • central nervous system • immunohistochemistry


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