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Presence of non-fibrillar amyloid β protein in skin biopsies of Alzheimer's disease (AD), Down's syndrome and non-AD normal persons

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Abstract

A total of 66 skin biopsies from persons with Alzheimer's disease (AD) or Down's syndrome (DS) and from persons without AD were used in this study. The age range was from 7 to 89 years. Positive immunoreactivity of skin biopsies to monoclonal antibody 4G8, which is reactive to amino acid residue 17–24 of synthetic amyloid β protein (Aβ), and 4G8-Fab (the antigen-binding fragment of 4G8 IgG, reactive only to amyloid plaque) was observed in the epidermis-dermis junction or the basement membrane of the epidermis and in some blood vessels of the biopsy skins of 13/18 (72%) AD, 9/10 (90%) DS, and 14/38 (37%) non-AD control cases. The Fisher exact probability test revealed a significant difference (P=0.0415 one-tailed) in immunoreactivity between AD and age-matched controls. There was also a significant difference (P=0.0152 one-tailed; P=0.0200 two-tailed) between DS and age-matched control in the same test. Immuno-gold electron microscopy examination of these cases with positive immunoreactivity revealed that the gold particles were deposited along the basement membrane of the epidermis. Amyloid fibrils were not observed in the regions with gold particles. Results of this study suggest that Aβ is associated with the basement membrane of skin and is present in amorphous, non-fibrillar form as soluble Aβ.

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Authors and Affiliations

  1. New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, 10314, Staten Island, NY, USA

    G. Y. Wen, H. M. Wisniewski, R. Rudelli & K. S. Kim

  2. University of Iceland Medical School, Vatnsmyrarveg 16, 101, Reykjavik, Iceland

    H. Blondal & E. Benedikz

  3. University of Tampere, SF-33520, Tampere, Finland

    H. Frey & T. Pirttila

Authors
  1. G. Y. Wen
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  2. H. M. Wisniewski
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  3. H. Blondal
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  4. E. Benedikz
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  5. H. Frey
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  6. T. Pirttila
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  7. R. Rudelli
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  8. K. S. Kim
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Additional information

Supported in part by funds from the New York State Office of Mental Retardation and Developmental Disabilities and grant nos. PO1-AGO-4220 and PO1-AG11531 from the National Institute on Aging, NIH and the fund for the center for trace metal studies and environmental neurotoxicology

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Wen, G.Y., Wisniewski, H.M., Blondal, H. et al. Presence of non-fibrillar amyloid β protein in skin biopsies of Alzheimer's disease (AD), Down's syndrome and non-AD normal persons. Acta Neuropathol 88, 201–206 (1994). https://doi.org/10.1007/BF00293394

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  • DOI: https://doi.org/10.1007/BF00293394

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