Publication Detail

The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.

Specific regional transcription of apolipoprotein E in human brain neurons.

P T Xu; J R Gilbert; H L Qiu; J Ervin; T R Rothrock-Christian; C Hulette; D E Schmechel (Profiled Authors: Schmechel, Donald E; Gilbert, John R)

Department of Medicine (Neurology), Duke University Medical Center, Durham, North Carolina 27710, USA. pxu@galactose.mc.duke.edu
The American journal of pathology 1999;154(2):601-11.

In central nervous system injury and disease, apolipoprotein E (APOE, gene; apoE, protein) might be involved in neuronal injury and death indirectly through extracellular effects and/or more directly through intracellular effects on neuronal metabolism. Although intracellular effects could clearly be mediated by neuronal uptake of extracellular apoE, recent experiments in injury models in normal rodents and in mice transgenic for the human APOE gene suggest the additional possibility of intraneuronal synthesis. To examine whether APOE might be synthesized by human neurons, we performed in situ hybridization on paraffin-embedded and frozen brain sections from three nondemented controls and five Alzheimer's disease (AD) patients using digoxigenin-labeled antisense and sense cRNA probes to human APOE. Using the antisense APOE probes, we found the expected strong hybridization signal in glial cells as well as a generally fainter signal in selected neurons in cerebral cortex and hippocampus. In hippocampus, many APOE mRNA-containing neurons were observed in sectors CA1 to CA4 and the granule cell layer of the dentate gyrus. In these regions, APOE mRNA containing neurons could be observed adjacent to nonhybridizing neurons of the same cell class. APOE mRNA transcription in neurons is regionally specific. In cerebellar cortex, APOE mRNA was seen only in Bergmann glial cells and scattered astrocytes but not in Purkinje cells or granule cell neurons. ApoE immunocytochemical localization in semi-adjacent sections supported the selectivity of APOE transcription. These results demonstrate the expected result that APOE mRNA is transcribed and expressed in glial cells in human brain. The important new finding is that APOE mRNA is also transcribed and expressed in many neurons in frontal cortex and human hippocampus but not in neurons of cerebellar cortex from the same brains. This regionally specific human APOE gene expression suggests that synthesis of apoE might play a role in regional vulnerability of neurons in AD. These results also provide a direct anatomical context for hypotheses proposing a role for apoE isoforms on neuronal cytoskeletal stability and metabolism.

2 Originating Grant

• 1.

  Schmechel, Donald E

  ALZHEIMER'S DISEASE RESEARCH CENTER

  1 May 2000 - 30 April 2005

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 16,537,307

• 2.

  ROSES, ALLEN D

  ALZHEIMERS DISEASE RESEARCH CENTER

  30 September 1985 - 30 April 2000

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 17,660,528

Scientific Context

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