Widespread distribution of PLTP in human CNS: evidence for PLTP synthesis by glia and neurons, and increased levels in Alzheimer's disease.
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.
Vuletic
Simona
S
Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Jin
Lee-Way
LW
Marcovina
Santica M
SM
Peskind
Elaine R
ER
Moller
Thomas
T
Albers
John J
JJ
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism*; D003470:Culture Media / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins; D012333:RNA, Messenger / Q000032:analysis
D002352:Carrier Proteins; D003470:Culture Media; D008074:Lipoproteins; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D012333:RNA, Messenger