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Letters to Nature
Nature 331, 528 - 530 (11 February 1988); doi:10.1038/331528a0

Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease

Rudolph E. Tanzi*, Andrea I. McClatchey*, Edward D. Lamperti§, Lydia Villa-Komaroff, James F. Gusella* & Rachael L. Neve||

*Neurogenetics Laboratory, Massachusetts General Hospital, and The Department of Genetics and The Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA
Division of Genetics, Department of Pediatrics and The Mental Retardation Research Center, The Children's Hospital; and The Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA
Division of Neuroscience and The Mental Retardation Research Center, The Children's Hospital; and Department of Neuropathology, Harvard Medical School, Boston, Massachusetts 02115, USA
§Department of Anatomy, University of Massachusetts Medical Center, Worcester, Massachusetts 01605, USA
||To whom correspondence should be addressed

Amyloid B-protein/amyloid A4 is a peptide present in the neuritic plaques, neurofibrillary tangles and cerebrovascular deposits in patients with Alzheimer's disease and Down's syndrome (trisomy 21)1–4 and may be involved in the pathogenesis of Alzheimer's disease5. Recent molecular genetic studies have indicated that amyloid protein is encoded as part of a larger protein by a gene on human chromosome 21 (refs 6–9). The amyloid protein precursor (APP) gene is expressed in brain and in several peripheral tissues, but the specific biochemical events leading to deposition of amyloid are not known. We have now screened complementary DNA libraries constructed from peripheral tissues to determine whether the messenger RNA encoding APP in these tissues is identical to that expressed in brain, and we identify a second APP mRNA that encodes an additional internal domain with a sequence characteristic of a Kunitz-type serine protease inhibitor. The alternative APP mRNA is present in both brain and peripheral tissues of normal individuals and those with Alzheimer's disease, but its pattern of expression differs from that of the previously reported APP mRNA.

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References

1. Glenner, G. G. & Wong, C. W. Biochem. biophys. Res. Commun. 122, 1131−1135 (1984). | Article | PubMed | ISI | ChemPort |
2. Kidd, M., Allsop, D. & Landon, M. Lancet i, 278 (1985).
3. Masters, C. L. et al. EMBO J. 4, 2757−2763 (1985). | PubMed | ISI | ChemPort |
4. Masters, C. L. et al. Proc. natn. Acad. Sci. U.S.A. 82, 4245−4249 (1985). | ChemPort |
5. Roch, M., Tomlinson, G. & Blessed, G. Nature 209, 109−110 (1966). | PubMed |
6. Tanzi, R. E. et al. Science 235, 880−885 (1987). | PubMed | ISI | ChemPort |
7. Kang, J. et al. Nature 325, 733−736 (1987). | Article | PubMed | ISI | ChemPort |
8. Goldgaber, D., Lerman, M. I., McBride, W., Saffiotti, U. & Gajdusek, D. C. Science 235, 877−879 (1987). | PubMed | ISI | ChemPort |
9. Robakis, N. K., Ramakrishna, N., Wolfe, G. & Wisniewski, H. M. Proc. natn. Acad. Sci. U.S.A. 84, 4190−4193 (1987). | ChemPort |
10. Tanzi, R. E. et al. Nature 329, 156−157 (1987). | Article | PubMed | ISI | ChemPort |
11. Kunitz, M. J. Gen. Physiol. 10, 311−320 (1947).
12. Hochstrasser, K., Schonberger, O. L., Rossmanith, I. Wachter, E. Hoppe-Seyler's Z. physiol. Chem. 362, 1357−1362 (1981). | ChemPort |
13. Kaumeyer, J. F., Polazzi, J. O. & Kotick, M. P. Nucleic Acids Res. 14, 7839−7850 (1986). | PubMed | ChemPort |
14. Hochstasser, K., Albrecht, G. J., Schonberger, O. I. & Wachter, E. Hoppe-Seyler's Z. physiol. Chem. 364, 1689−1696 (1983).
15. Fioretti, E., Iacopino, G., Angeletti, M., Barra, D. & Ascoli, F. J. biol. Chem. 260, 11451−11455 (1985). | PubMed | ChemPort |
16. Albrecht, G. J. Hochstrasser, K. & Salier, J.Ph. Hoppe-Seyler's Z. physiol. Chem. 364, 1703−1708 (1983). | ChemPort |
17. Bromke, B. J. & Kueppers, F. Biochem. Med. 27, 56−67 (1982). | Article | PubMed | ChemPort |
18. Hochstrasser, K., Reisinger, P., Albrecht, G. J., Wachter, E. & Schonberger, O. L. Hoppe-Seyler's Z. physiol. Chem. 365, 1123−1130 (1984). | PubMed | ChemPort |
19. Reisinger, P., Hochstrasser, K., Albrecht, G. J., Lempart, K. & Salier, J.Ph. Biol. chem. Hoppe-Seyler 366, 479−483 (1985). | PubMed | ChemPort |
20. Ghiso, J., Jensson, O. & Frangione B. Proc. natn. Acad. Sci. U.S.A. 83, 2974−2978 (1986). | ChemPort |
21. Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad Sci. U.S.A. 74, 5463−5467 (1977). | ChemPort |
22. Tabor, S. & Richardson, C. C. Proc. natn. Acad. Sci. U.S.A. 84, 4767−4771 (1987). | ChemPort |
23. Travis, J. & Salvesen, G. S. A. Rev. Biochem. 52, 655−709 (1983). | Article | ISI | ChemPort |
24. Anderson, S. & Kingston, B. I. Proc. natn. Acad. Sci. U S.A. 80, 6838−6842 (1983). | ChemPort |
25. Wachter, E. & Hochstrasser, K. Hoppe-Seyler's Z. physiol. Chem. 362, 1351−1355 (1981). | ChemPort |
26. Takahashi, H., Iwanaga, S., Kitagawa, T., Hokama, Y. & Suzuki, T. J. Biochem., Tokyo 76, 721−733 (1974). | ChemPort |
27. Tschesche, H. & Dietl, T. Eur. J. Biochem. 58, 439−451 (1975). | Article | PubMed | ChemPort |
28. Neve, R. L., Harris, P., Kosik, K. S., Kurnit, D. M. & Donlon, T. A. Molec. Brain Res. 1, 271−280 (1986). | Article | ChemPort |



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