β-Amyloid-Protein Immunoreactivity in Skin is Not a Reliable Marker of Alzheimer’s Disease: An Autopsy Controlled Study

  • Outi Heinonen
  • Hilkka Soininen
  • Stina Syrjänen
  • Heikki Neittaanmäki
  • Leo Paljärvi
  • Olli Kosunen
  • Sakari Talasniemi
  • Kari Syrjänen
  • Paavo RiekkinenSr.
Part of the Advances in Behavioral Biology book series (ABBI, volume 44)

Abstract

Recent studies have shown that the process underlying β/A4 deposition in AD is not restricted to the brain. Soluble β/A4 species have been isolated and quantified in the cerebrospinal fluid and plasma.1 Small deposits immunopositive for β/A4 have been detected in and around selected blood vessels of the skin, intestine and certain other tissues from some patients with AD and Down’s syndrome (DS) as well as in a proportion of aged normal subjects.2 Such observations in nonneuronal tissues might provide clues to pathogenetic mechanisms and treatment of AD and could prove useful in confirming the clinical diagnosis of AD. Diagnostic markers are urgently needed in AD. This study was therefore aimed at investigating the usefulness of β/A4 immunostaining of skin biopsies to diagnose AD. Preliminary results of β/A4 immunoreactivity in skin in aging and dementia have been presented as a letter elsewhere.3 In the present work, the correlation between β/A4 immunopositivity in lifetime skin biopsy and brain of neuropathologically confirmed AD patients was examined. Further, the β/A4 immunopositivity in skin of DS patients and young controls was studied.

Keywords

Lewy Body Dementia Vascular Basement Membrane Ischemic Score Dermal Blood Vessel Endothelial Staining 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    P. Seubert, C. Vigo-Pelfrey, F. Esch, M. Lee, H. Dovey, D. Davis, S. Sinha, M. Schlossmacher, J. Whaley, C. Swindlehurst, R. McCormack, R. Wolfert, D. Selkoe, I. Lieberburg, D. Schenk, Isolation and quantification of soluble Alzheimer’s ß-peptide from biological fluids, Nature 359: 325327 (1992).Google Scholar
  2. 2.
    C. Joachim, H. Mori, and D. Selkoe. Amyloid beta-protein deposition in tissues other than brain in Alzheimer’s disease, Nature 341: 226–230 (1989).Google Scholar
  3. 3.
    H. Soininen, S. Syrjinen, O. Heinonen, H. Neittaanmi, R. Miettinen, L. Paljiirvi, K. Syrjiïnen, K. Beyreuther, P. Riekkinen. Amyloid-ß-protein deposition in skin of patients with dementia, Lancet 339: 245 (1992).Google Scholar
  4. 4.
    G. McKhann, D. Drachman, M. Folstein, R. Katzman, D. Price, and E.M. Stadlan. Clinical diagnosis of Alzheimer’s disease: a report of NINCDS-ADRDA work group under auspices of Department of Health and Human Services Task Force on Alzheimer’s disease, Neurology 34: 939–944 (1984).Google Scholar
  5. 5.
    American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 3rd ed., Washington (1980).Google Scholar
  6. 6.
    M.F. Folstein, S.E. Folstein, and P.R. McHugh. Mini-Mental-State. A practical method for grading cognitive state of patients for the clinician, J. Psychiatr. Res. 12: 189–198 (1975).Google Scholar
  7. 7.
    G. Blessed, B.E. Tomlinson, and M. Roth. The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects, Br. J. Psychiatry 114: 797811 (1968).Google Scholar
  8. 8.
    W.G. Rosen, R.D. Terry,P.A. Fuld, R. Katzman, and A. Peck. Pathologcal verification of ischaemic score in differentiation of dementias, Ann. Neurol. 7: 486–488 (1980).Google Scholar
  9. 9.
    S.S. Mirra, A. Heyman, D. McKeel, S.M. Sumi, B.J. Crain, L.M. Brownlee, F.S. Vogel, J.P. Hughes, G. van Belle, L. Berg, and participating CERAD neuropathologists. The consortium to establish a registry for Alzheimer’s disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease, Neurology 41: 479–486 (1991).Google Scholar
  10. 10.
    R.H. Perry, D. Irving, G. Blessed, A. Fairbaim, and E. Perry. Senile dementia of Lewy body type: A clinically and neuropathologically distinct form of Lewy body dementia in the elderly, J. Neurol. Sci. 95: 119–13 (1990).Google Scholar
  11. 11.
    M. Ikeda, M. Shoji, H. Yamaguchi, E. Matsubara, M. Amari, K. Ishiguro, T. Kawarabayashi, Y. Harigaya, S. Hirai, Diagnostic significance of skin immunolabelling with antibody against native cerebral amyloid in Alzheimer’s disease, Neurosci. Lett. 150: 59–161 (1993).Google Scholar
  12. 12.
    H. Arai, V.M.-Y. Lee, M.L. Messinger, B.D. Greenberg, D.E. Lowery, and J.Q. Trojanowski. Expression patterns of ß-amyloid precursor protein (ft-APP) in neural and nonneural human tissues from Alzheimer’s disease and control subjects, Ann. Neurol. 30: 686–693 (1991).Google Scholar
  13. 13.
    B. Rumble, R. Retallack, C. Hilbich, G. Simms, G. Multhaup, R. Martins, A. Hockey, P. Montgomery, K. Beyreuther, C.L. Masters, Amyloid A4 protein and its precursor in Down’s syndrome and Alzheimer’s disiwce, N. Engl. J. Med. 320: 1446–1452 (1989).Google Scholar
  14. 14.
    M.B. Podlisny, A.L. Mammen, M.G. Schlossmacher, M.R. Palmeri, S.G. Younkin, and D.J. Selkoe. Detection of soluble forms of the ß-amyloid precursor protein in human plasma, Biochem. Biophys. Res. Commun. 167: 1094–1101 (1990).Google Scholar
  15. 15.
    A.I. Bush, R.N. Martins, and B. Rumble. The amyloid precursor protein of Alzheimer’s dissAsf• is released by human platelets, J. Biol. Chem. 265: 15977–15983 (1990).Google Scholar
  16. 16.
    M.G. Schlossmacher, B.L. Ostaszewski, and L.I. Hecker. Detection of distinct isoform patterns of the ß-amyloid precursor protein in human platelets and lymphocytes, Neurobiol. Aging 13: 421434 (1992).Google Scholar
  17. 17.
    C. Haass, A. Hung, and D. Selkoe. Processing of ß-amyloid precursor protein in microglia and astrocytes favors an internal localization over constitutive secretion. J. Neurosci. 11: 37833793 (1991).Google Scholar
  18. 18.
    R. Neve, E. Finch, and L. Dawes. Expression of the Alzheimer amyloid precursor gene transcripts in the human brain, Neuron 1: 669–677 (1988).Google Scholar
  19. 19.
    D. Schmechel, D. Goldgaber, D. Burkhart, J. Gilbert, D. Gajdusek, and A. Roses. Cellular localization of messenger RNA encoding amyloid-beta-protein in normal tissue and in Alzheimer’s disease, Alzheimer Dis. Assoc. Disord. 2: 96–111 (1988).Google Scholar
  20. 20.
    F. Tagliavini, J. Ghiso, W. Timmers, G. Giaccone, O. Bulgiani, and B. Frangione. Coexistence of Alzheimer’s amyloid precursor protein and amyloid protein in cerebral vessel walls, Lab. Invest. 62: 761–767 (1990).Google Scholar
  21. 21.
    L.S. Perlmutter, and H. Chang Chui. Microangiopathy, the vascular basement membrane and Alzheimer’s disease; a review, Brain Res. Bull. 24: 677–686 (1990).Google Scholar
  22. 22.
    A.B. Scheibel, T. Duong, and U. Tomiyasu. Denervation microangiopathy in senile dementia, Alzheimer type Alzheimer Dis. Assoc. Disord. 1:19–37(1987).Google Scholar
  23. 23.
    R. Katzman, and T. Saitoh. Advances in Alzheimers disease, FASEB J. 5: 278–286 (1991).Google Scholar
  24. 24.
    K. Abe, R.E. Tanzi, and K. Kogure. Selective induction of Kunitz-type protease inhibitor domain-containing amyloid precursor protein mRNA after persistent focal ischemia in rat cerebral cortex, Neurosci. Leu. 125: 172–174 (1991).Google Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Outi Heinonen
    • 1
  • Hilkka Soininen
    • 1
  • Stina Syrjänen
    • 2
  • Heikki Neittaanmäki
    • 3
  • Leo Paljärvi
    • 2
  • Olli Kosunen
    • 2
  • Sakari Talasniemi
    • 4
  • Kari Syrjänen
    • 2
  • Paavo RiekkinenSr.
    • 1
    • 5
  1. 1.Departments of NeurologyUniversity of KuopioFinland
  2. 2.Departments of PathologyUniversity of KuopioFinland
  3. 3.Departments of DermatologyUniversity of KuopioFinland
  4. 4.Harjula Hospital, KuopioKuopioFinland
  5. 5.A.I. Virtanen InstituteUniversity of KuopioFinland

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