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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.
Keywords
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Article info
Publication history
Received in revised form:
October 14,
1993
Received:
June 2,
1993
Footnotes
☆This research was supported in part through a cooperative research and development agreement with Molecular Geriatrics Corp. (Lake Bluff, IL).
Identification
Copyright
© 1993 Published by Elsevier Inc.