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The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor

Nature volume 325, pages 733–736 (1987)Cite this article

Abstract

Alzheimer's disease1 is characterized by a widespread functional disturbance of the human brain. Fibrillar amyloid proteins are deposited inside neurons as neurofibrillary tangles2 and extracel-lularly as amyloid plaque cores2 and in blood vessels2. The major protein subunit (A4) of the amyloid fibril of tangles, plaques and blood vessel deposits is an insoluble, highly aggregating small polypeptide of relative molecular mass 4,5003–6. The same polypep-tide is also deposited in the brains of aged individuals with trisomy 21 (Down's syndrome)3,5,6. We have argued previously that the A4 protein is of neuronal origin and is the cleavage product of a larger precursor protein4,6. To identify this precursor, we have now isolated and sequenced an apparently full-length complementary DNA clone coding for the A4 polypeptide. The predicted precursor consists of 695 residues and contains features characteristic of glycosylated cell-surface receptors. This sequence, together with the localization of its gene on chromosome 21, suggests that the cerebral amyloid deposited in Alzheimer's disease and aged Down's syndrome is caused by aberrant catabolism of a cell-surface receptor.

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Author notes

  1. Colin L. Masters: Neuromuscular Research Institute, Department of Pathology, University of Western Australia, Perth, 6009 Western Australia and Department of Neuropathology, Royal Perth Hospital, Perth, 6001 Western Australia

  2. Karl-Heinz Grzeschik: Institut für Humangenetik, Westfälische Wilhelms Universität Münster, FRG

Authors and Affiliations

  1. Institut für Genetik der Universität zu Köln, Weyertal 121, D-5000, Köln, 41, FRG

    Jie Kang, Hans-Georg Lemaire, Axel Unterbeck, J. Michael Salbaum, Colin L. Masters, Karl-Heinz Grzeschik, Gerd Multhaup, Konrad Beyreuther & Benno Müller-Hill

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  1. Jie Kang
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  2. Hans-Georg Lemaire
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  3. Axel Unterbeck
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  4. J. Michael Salbaum
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  6. Karl-Heinz Grzeschik
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  7. Gerd Multhaup
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  8. Konrad Beyreuther
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  9. Benno Müller-Hill
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Kang, J., Lemaire, HG., Unterbeck, A. et al. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature 325, 733–736 (1987). https://doi.org/10.1038/325733a0

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