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Journal of Lipid Research, Vol. 44, 1113-1123, June 2003 Widespread distribution of PLTP in human CNS: evidence for PLTP synthesis by glia and neurons, and increased levels in Alzheimer's disease
* Department of Medicine, University of Washington, Seattle, WA 98195
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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