Olfactory neuroblasts from Alzheimer donors: Studies on APP processing and cell regulation

Benjamin Wolozin, Peter Lesch, Robert Lebovics, Trey Sunderland

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Cell lines of continuously dividing human olfactory neuroblasts can be propagated using olfactory epithelium obtained from human donors at biopsy or autopsy. The expression of neuronal proteins in these cells, such as neurofilament protein and tau proetin, can be increased using a combination of factors including nerve growth factor, fibroblast growth factor, interleukin 1 and interleukin 6. These cells also express aspects of human disease. Olfactory neuroblasts generated from donors with the common, sporadic forms of Alzheimer's disease, show elevated levels of the direct precursor to β-amyloid, the amyloid precursor protein C-terminal derivative (CTD). When treated with the lysosomal inhibitor chloroquine, immunoblots of Alzheimer olfactory neuroblasts show seven-fold higher levels of CTDs than immunoblots from age-matched control neuroblasts. The disease related increases in CTDs can be reversed by treatment with agents that increase intracellular cyclic adenosine monophosphate (cAMP), such as dibutyril-cyclic-AMP, theophylline, and isoproteronol.

Original languageEnglish
Pages (from-to)824-838
Number of pages15
JournalBiological Psychiatry
Volume34
Issue number12
DOIs
StatePublished - 15 Dec 1993
Externally publishedYes

Keywords

  • Amyloid
  • NGF
  • cAMP
  • electrophoresis
  • lysosome

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