Specific regional transcription of apolipoprotein E in human brain neurons

Xu Pu-Ting, John Gilbert, Qiu Hui-Ling, John Ervin, Tracie R. Rothrock-Christian, Christine Hulette, Donald E. Schmechel

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)601-611
Number of pages11
JournalAmerican Journal of Pathology
Volume154
Issue number2
StatePublished - Feb 1 1999
Externally publishedYes

Fingerprint

Apolipoproteins E
Neurons
Brain
Messenger RNA
Neuroglia
Hippocampus
Cerebellar Cortex
Alzheimer Disease
Nervous System Trauma
Digoxigenin
Complementary RNA
Purkinje Cells
Central Nervous System Diseases
Dentate Gyrus
Wounds and Injuries
Frozen Sections
Frontal Lobe
Astrocytes
Cerebral Cortex
Paraffin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Pu-Ting, X., Gilbert, J., Hui-Ling, Q., Ervin, J., Rothrock-Christian, T. R., Hulette, C., & Schmechel, D. E. (1999). Specific regional transcription of apolipoprotein E in human brain neurons. American Journal of Pathology, 154(2), 601-611.

Specific regional transcription of apolipoprotein E in human brain neurons. / Pu-Ting, Xu; Gilbert, John; Hui-Ling, Qiu; Ervin, John; Rothrock-Christian, Tracie R.; Hulette, Christine; Schmechel, Donald E.

In: American Journal of Pathology, Vol. 154, No. 2, 01.02.1999, p. 601-611.

Research output: Contribution to journalArticle

Pu-Ting, X, Gilbert, J, Hui-Ling, Q, Ervin, J, Rothrock-Christian, TR, Hulette, C & Schmechel, DE 1999, 'Specific regional transcription of apolipoprotein E in human brain neurons', American Journal of Pathology, vol. 154, no. 2, pp. 601-611.
Pu-Ting X, Gilbert J, Hui-Ling Q, Ervin J, Rothrock-Christian TR, Hulette C et al. Specific regional transcription of apolipoprotein E in human brain neurons. American Journal of Pathology. 1999 Feb 1;154(2):601-611.
Pu-Ting, Xu ; Gilbert, John ; Hui-Ling, Qiu ; Ervin, John ; Rothrock-Christian, Tracie R. ; Hulette, Christine ; Schmechel, Donald E. / Specific regional transcription of apolipoprotein E in human brain neurons. In: American Journal of Pathology. 1999 ; Vol. 154, No. 2. pp. 601-611.
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