Abstract
ALZHEIMER'S disease is the most common cause of progressive intellectual failure in aged humans. The filamentous brain lesions which define the disease occur within neurons (neurofibrillary tangles), in extracellular cerebral deposits (amyloid plaques) and in meningocerebral blood vessels (amyloid angiopathy)1,2. They are found in lesser numbers in the brains of virtually all old humans1. A protein with a relative molecular mass (Mr) of ∼4,000, designated amyloid β-protein or amyloid A4 protein, is the subunit of the vascular and plaque amyloid filaments in individuals with Alzheimer's disease3–5, normal ageing6 and trisomy 21 (Down's syndrome) 7. The amyloid β-protein is a small fragment of a membrane-associated glycoprotein8–13, encoded by a gene on human chromosome 21 which is telomeric to a genetic defect that causes at least some cases of familial Alzheimer's disease14,15. Until now, the pathological lesions of the disease have been found only in the brain, although reports of phenotypic abnormalities in non-neural tissues16–20 have suggested that Alzheimer's disease may be a widespread, systemic disorder. Here we report the detection of amyloid β-protein deposits in non-neural tissues and blood vessels of Alzheimer's disease patients, including skin, subcutaneous tissue and intestine. The protein was also present in non-neural tissues in a proportion of aged, normal subjects. Our findings indicate that a principal feature of the disease process is expressed subclinically in tissues other than brain. The occurrence of amyloid β- protein deposits in multiple tissues suggests that the protein may be produced locally in numerous organs or may, as in other human amyloidoses, be derived from a common circulating precursor. These observations affect the rationale for many experiments analysing the amyloid β-protein precursor and its messenger RNAs in Alzheimer's disease brain tissue and have major implications for the pathogenesis and treatment of the disease.
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References
Tomlinson, B. E. & Corsellis, J. A. N. in Greenfield' Neuropathology (eds Adams, J. H., Corsellis, J. A. N. & Duchen, L. W.) 951–1025 (Arnold, London, 1984).
Anderton, B. H. Nature 325, 658–659 (1987).
Glenner, G. G. & Wong, C. W. Biochem. biophys. Res. Commun. 120, 885–890 (1984).
Masters, C. L. et al. Proc. natn. Acad. Sci. U.S.A. 82, 4245–4249 (1985).
Selkoe, D. J., Abraham, C. R., Podlisny, M. B. & Duffy, L. K. J. Neurochem. 46, 1820–1834 (1986).
Coria, F., Castano, E. M. & Frangione, B. Am. J. Path. 129, 422–428 (1988).
Glenner, G. G. & Wong, C. W. Biochem. biophys. Res. Commun. 122, 1131–1135 (1984).
Kang, J. et al. Nature 325, 733–736 (1987).
Ponte, P. et al. Nature 331, 525–527 (1988).
Tanzi, R. E. et al. Nature 331, 528–530 (1988).
Kitaguchi, N., Takahashi, Y., Tokushima, Y., Shiojiri, S. & Ito, H. Nature 331, 530–532 (1988).
Selkoe, D. J. et al. Proc. natn. Acad. Sci. U.S.A. 85, 7341–7345 (1988).
Weidemann, A. et al. Cell 57, 115–126 (1989).
St. George-Hyslop, P. H. et al. Science 238, 664–666 (1987).
Goate, A. M. et al. Lancet 352–355 (1989).
Markesbery, W. R., Leung, P. K. & Butterfield, D. A. J. Neurol. Sci. 45, 323–330 (1980).
Peterson, C., Gibson, G. E. & Blass, J. P. N. Engl. J. Med. 312, 1063–1065 (1985).
Scudiero, D. A. et al. Mutat. Res. 159, 125–131 (1986).
Peterson, C. & Goldman, J. E. Proc. natn. Acad. Sci. U.S.A. 83, 2758–2762 (1986).
Zubenko, G. S., Wusylko, M., Cohen, B. M., Boller, F. & Teply, I. Science 238, 539–542 (1987).
Tagliavani, F., Giaccone, G., Frangione, B. & Bugiani, O. Neurosci. Lett. 93, 191–196 (1988).
Yamaguchi, H., Hirai, S., Morimatsu, M., Shoji, M. & Harigaya, Y. Acta Neuropath. 76, 541–549 (1988).
Mann, D. & Esiri, M. M. N. Engl. J. Med. 318, 789 (1988).
Joachim, C. L., Morris, J. & Selkoe, D. J. Am. J. Path. 135, 309–319 (1989).
Glenner, G. G. in Banbury Report: Biological Aspects of Alzheimer's Disease (ed. Katzman, R.) 137–144 (Cold Spring Harbor Laboratory, New York, 1983).
Selkoe, D. J. Neurobiol. Aging 7, 425–432 (1986).
Eikelenboom, P., & Stam, F. C. Acta Neuropath. 57, 2139–2142 (1982).
Abraham, C. R., Selkoe, D. J. & Potter, H. Cell 52, 487–501 (1988).
Coria, F. et al. Lab. Invest. 58, 454–458 (1988).
Hart, M. N. et al. Am. J. Path. 132, 167–172 (1988).
Joachim, C. L., Duffy, L. K., Morris, J. H. & Selkoe, D. J. Brain Res. 474, 100–111 (1988).
Selkoe, D. J., Bell, D. S., Podlisny, M. B., Price, D. L. & Cork, L. C. Science 235, 873–877 (1987).
Ihara, Y., Abraham, C. & Selkoe, D. J. Nature 304, 727–730 (1983).
Dahl, D. & Bignami, A. Brain Res. 57, 343–360 (1973).
Shirahama, T., Cohen, A. S. & Skinner, M. in Advances in Immunohistochemistry (ed. DeLellis, R. A.) 277–302 (Masson, New York, 1984).
Ju, S.-T., Skinner, M., Shirahama, T. & Cohen, A. S. Fedn Proc. 46, 1326 (1987).
Van Duinen, S. G. et al. Proc. natn. Acad. Sci. U.S.A. 84, 5991–5994 (1987).
Kitamoto, T., Ogomori, K., Tateishi, J. & Prusiner, S. B. Lab. Invest. 57, 230–236 (1987).
Blöndal, H., Guomundsson, G., Benedikz, E. & Johannesson, G. Alzheimer' Dis. Assoc. Dis. 2, 170 (1988).
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Joachim, C., Mori, H. & Selkoe, D. Amyloid β-protein deposition in tissues other than brain in Alzheimer's disease. Nature 341, 226–230 (1989). https://doi.org/10.1038/341226a0
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DOI: https://doi.org/10.1038/341226a0
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