Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 Sep;86(3):1004–1013. doi: 10.1172/JCI114762

Enhanced expression of an exocrine pancreatic protein in Alzheimer's disease and the developing human brain.

S M de la Monte 1, M Ozturk 1, J R Wands 1
PMCID: PMC296822  PMID: 2394826

Abstract

Pancreatic thread protein (PTP) is a major exocrine secretory protein that in vitro forms filamentous bundles reminiscent of the paired helical filaments of Alzheimer's disease (AD). We previously described increased PTP immunoreactivity in AD brains and now report high levels in the developing human brain. Using a full-length cloned bovine PTP cDNA and synthetic oligonucleotides corresponding to human PTP cDNA, which is identical to human islet cell regeneration factor, we analyzed the expression of PTP in pancreas and brain. A major 0.9-kb as well as several minor transcripts were identified in human pancreas. In AD brain, the same size transcripts were detected by Northern analysis, primer extension assay, or polymerase chain reaction amplification of cDNAs generated by reverse transcriptase assay. There were significantly higher levels of PTP mRNA in brains with AD compared with aged controls, with increased amounts of 1.2-, 0.6-, and 0.4-kb transcripts by Northern analysis. In situ hybridization localized expression to pyramidal neurons in the cerebral cortex, the same population that contains neurofibrillary tangles and high levels of immunoreactive PTP. These findings suggest that AD is associated with enhanced expression of PTP-related transcripts with intraneuronal accumulation of PTP-like proteins.

Full text

PDF
1004

Images in this article

1007Image
on p.1007
1008Image
on p.1008
1009Image
on p.1009
1009Image
on p.1009
1009Image
on p.1009
1010Image
on p.1010
1010Image
on p.1010
1010Image
on p.1010
1010Image
on p.1010
1010Image
on p.1010
1010Image
on p.1010
1011Image
on p.1011
1011Image
on p.1011
1011Image
on p.1011
1011Image
on p.1011
1011Image
on p.1011

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Awgulewitsch A., Utset M. F., Hart C. P., McGinnis W., Ruddle F. H. Spatial restriction in expression of a mouse homoeo box locus within the central nervous system. 1986 Mar 27-Apr 2Nature. 320(6060):328–335. doi: 10.1038/320328a0. [DOI] [PubMed] [Google Scholar]
  2. Chehab F. F., Doherty M., Cai S. P., Kan Y. W., Cooper S., Rubin E. M. Detection of sickle cell anaemia and thalassaemias. Nature. 1987 Sep 24;329(6137):293–294. doi: 10.1038/329293b0. [DOI] [PubMed] [Google Scholar]
  3. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  4. Cox K. H., DeLeon D. V., Angerer L. M., Angerer R. C. Detection of mrnas in sea urchin embryos by in situ hybridization using asymmetric RNA probes. Dev Biol. 1984 Feb;101(2):485–502. doi: 10.1016/0012-1606(84)90162-3. [DOI] [PubMed] [Google Scholar]
  5. De Caro A. M., Bonicel J. J., Rouimi P., De Caro J. D., Sarles H., Rovery M. Complete amino acid sequence of an immunoreactive form of human pancreatic stone protein isolated from pancreatic juice. Eur J Biochem. 1987 Oct 1;168(1):201–207. doi: 10.1111/j.1432-1033.1987.tb13405.x. [DOI] [PubMed] [Google Scholar]
  6. Gross J., Brauer A. W., Bringhurst R. F., Corbett C., Margolies M. N. An unusual bovine pancreatic protein exhibiting pH-dependent globule-fibril transformation and unique amino acid sequence. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5627–5631. doi: 10.1073/pnas.82.17.5627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gross J., Carlson R. I., Brauer A. W., Margolies M. N., Warshaw A. L., Wands J. R. Isolation, characterization, and distribution of an unusual pancreatic human secretory protein. J Clin Invest. 1985 Dec;76(6):2115–2126. doi: 10.1172/JCI112216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jones K. A., Yamamoto K. R., Tjian R. Two distinct transcription factors bind to the HSV thymidine kinase promoter in vitro. Cell. 1985 Sep;42(2):559–572. doi: 10.1016/0092-8674(85)90113-8. [DOI] [PubMed] [Google Scholar]
  9. Kemp D. J., Cowman A. F. Direct immunoassay for detecting Escherichia coli colonies that contain polypeptides encoded by cloned DNA segments. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4520–4524. doi: 10.1073/pnas.78.7.4520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kogan S. C., Doherty M., Gitschier J. An improved method for prenatal diagnosis of genetic diseases by analysis of amplified DNA sequences. Application to hemophilia A. N Engl J Med. 1987 Oct 15;317(16):985–990. doi: 10.1056/NEJM198710153171603. [DOI] [PubMed] [Google Scholar]
  11. Lehrach H., Diamond D., Wozney J. M., Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. doi: 10.1021/bi00640a033. [DOI] [PubMed] [Google Scholar]
  12. Meinkoth J., Wahl G. Hybridization of nucleic acids immobilized on solid supports. Anal Biochem. 1984 May 1;138(2):267–284. doi: 10.1016/0003-2697(84)90808-x. [DOI] [PubMed] [Google Scholar]
  13. Ozturk M., de la Monte S. M., Gross J., Wands J. R. Elevated levels of an exocrine pancreatic secretory protein in Alzheimer disease brain. Proc Natl Acad Sci U S A. 1989 Jan;86(2):419–423. doi: 10.1073/pnas.86.2.419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Reed K. C., Mann D. A. Rapid transfer of DNA from agarose gels to nylon membranes. Nucleic Acids Res. 1985 Oct 25;13(20):7207–7221. doi: 10.1093/nar/13.20.7207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  17. Terazono K., Yamamoto H., Takasawa S., Shiga K., Yonemura Y., Tochino Y., Okamoto H. A novel gene activated in regenerating islets. J Biol Chem. 1988 Feb 15;263(5):2111–2114. [PubMed] [Google Scholar]
  18. Terry R. D., Katzman R. Senile dementia of the Alzheimer type. Ann Neurol. 1983 Nov;14(5):497–506. doi: 10.1002/ana.410140502. [DOI] [PubMed] [Google Scholar]
  19. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Watanabe T., Yonekura H., Terazono K., Yamamoto H., Okamoto H. Complete nucleotide sequence of human reg gene and its expression in normal and tumoral tissues. The reg protein, pancreatic stone protein, and pancreatic thread protein are one and the same product of the gene. J Biol Chem. 1990 May 5;265(13):7432–7439. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES