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

β-Amyloid Protein Immunoreactivity in Skin Is Not a Reliable Marker of Alzheimer's Disease: An... Abstract Objectives: As a possible diagnostic marker for Alzheimer's disease (AD), we investigated β-amyloid protein (β/A4) immunoreactivity in skin. Furthermore, we studied the presence of β-amyloid precursor protein 695 immunoreactivity in skin. Design: Lifetime skin biopsy specimens were stained for β/A4 and β-amyloid precursor protein 695. The follow-up period was 12 months. We determined the correlation between β/A4 immunoreactivity in skin and brain in patients with a neuropathologic diagnosis. Setting: All patients with dementia were hospitalized; most of them had moderate to severe dementia. Aged nondemented controls were residents of a nursing home. The Down's syndrome (DS) group included both hospitalized and ambulatory patients. Young nondemented controls were medical students or staff members who volunteered for the study. Patients and Other Participants: The study included a total of 111 subjects. Thirty-five patients had probable AD, nine had possible AD, 15 had multiinfarct dementia, one had idiopathic Parkinson's disease, and one had Parkinson's disease and possible AD. There were also 19 elderly nondemented controls, 23 patients with DS, and eight young nondemented controls. Main Outcome Measures: Immunohistochemical detection of β/A4 in skin and correlation to the diagnosis of AD. Results: Immunopositivity for β/A4 antibody was present in and around the endothelium of dermal blood vessels in a proportion of patients with AD and multi-infarct dementia as well as elderly controls. The patients with sporadic AD displayed β/A4 immunoreactivity significantly more frequently than did patients with familial AD, patients with multi-infarct dementia, and controls. The β/A4 immunopositivity in skin was rare in the patients with DS and not present in young controls. Instead, 48% of patients with DS but none of other groups had β-amyloid precursor protein 695 immunoreactivity in skin. Only four (31%) of 13 patients with neuropathologically confirmed AD had shown endothelial β/A4 immunopositivity in skin biopsy specimens while alive. Conclusion: Our results do not support β/A4 as a diagnostic marker for AD. References 1. Goedert M. Neuronal localization of amyloid beta protein precursor mRNA in normal human brain and in Alzheimer's disease . EMBO J . 1987;235:3627-3632. 2. Kang J, Lemaire H-G, Unterbeck A, et al. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor . Nature . 1987;325:733-736.Crossref 3. Oltersdorf T, Friz LC, Schenk DB. The secreted form of Alzheimer amyloid precursor protein with the Kunitz domain is protease nexin-II . Nature . 1989:341: 144-147. 4. Glenner GG. Alzheimer's disease: its proteins and genes . Cell . 1988;52:307-308.Crossref 5. Müller-Hill B, Beyreuther K. Molecular biology of Alzheimer's disease . Annu Rev Biochem . 1989;58:287-307.Crossref 6. Tanzi RE, Gusella JF, Watkins PC, et al. Amyloid β protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus . Science . 1987;235: 860-864.Crossref 7. Palmert MR, Usiak M, Mayeux R, Raskind M, Tourtellotte WW, Younkin SG. Soluble derivatives of the β amyloid protein precursor in cerebrospinal fluid: alterations in normal aging and in Alzheimer's disease . Neurology . 1990;40: 1028-1034.Crossref 8. Podlisny MB, Mammen AL, Schlossmacher MG, Palmert MR, Younkin SG, Selkoe DJ. Detection of soluble forms of the β-amyloid precursor protein in human plasma . Biochem Biophys Res Commun . 1990;167:1094-1101.Crossref 9. Joachim C, Mori H, Selkoe D. Amyloid beta-protein deposition in tissues other than brain in Alzheimer's disease . Nature . 1989;341:226-230.Crossref 10. Soininen H, Syrjänen S, Heinonen O, et al. Amyloid-β-protein deposition in skin of patients with dementia . Lancet . 1992;339:245.Crossref 11. Mann DMA. The pathological association between Down syndrome and Alzheimer's disease . Mech Ageing Dev . 1988;43:99-136.Crossref 12. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. 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 . 1984;34:939-944.Crossref 13. American Psychiatric Association, Committee on Nomenclature and Statistics. Diagnostic and Statistical Manual of Mental Disorders , Third Edition. Washington, DC: American Psychiatric Association; 1980. 14. Folstein MF, Folstein SE, McHugh PR. Mini-Mental State: a practical method for grading cognitive state of patients for the clinician . J Psychiatr Res . 1975; 12:189-198.Crossref 15. Blessed G, Tomlinson BE, Roth M. The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects . Br J Psychiatry . 1968;114:797-811.Crossref 16. Rosen WG, Terry RD, Fuld PA, Katzman R, Peck A. Pathological verification of ischemic score in differentiation of dementias . Ann Neurol . 1980;7:486-488.Crossref 17. Mirra SS, Heyman A, McKeel D, et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD), II: standardization of the neuropathologic assessment of Alzheimer's disease . Neurology . 1991;41:479-486.Crossref 18. Bielschowsky M. Die Silberimpragnation der Axenzylinder . Centralplatt Neurol . 1902;22:579. 19. Bennhold H. Eine spesifische Amyloidfärbung mit Kangorot . Munch Med Wochenschr . 1922;33:1537. 20. Perry RH, Irving D, Blessed G, Fairbairn A, Perry E. Senile dementia of Lewy body type: a clinically and neuropathologically distinct form of Lewy body dementia in the elderly . J Neurol Sci . 1990;95:119-139.Crossref 21. Ikeda M, Shoji M, Yamaguchi H, et al. Diagnostic significance of skin immunolabelling with antibody against native cerebral amyloid in Alzheimer's disease . Neurosci Lett . 1993;150:159-161.Crossref 22. Haass C, Hung A, Selkoe D. Processing of β-amyloid precursor protein in micorglia and astrocytes favors an internal localization over constitutive secretion . J Neurosci . 1991;11:3783-3793. 23. Neve R, Finch E, Dawes L. Expression of the Alzheimer amyloid precursor gene transcripts in the human brain . Neuron . 1988;1:669-677.Crossref 24. Schmechel D, Goldgaber D, Burkhart D, Gilbert J, Gajdusek D, Roses A. Cellular localization of messenger RNA encoding amyloid-beta-protein in normal tissue and in Alzheimer's disease . Alzheimer Dis Assoc Disord . 1988;2:96-111.Crossref 25. Bush Al, Martins RN, Rumble B. The amyloid precursor protein of Alzheimer's disease is released by human platelets . J Biol Chem . 1990;265:15977-15983. 26. Schlossmacher MG, Ostaszewski BL, Hecker LI. Detection of distinct isoform patterns of the β-amyloid precursor protein in human platelets and lymphocytes . Neurobiol Aging . 1992;13:421-434.Crossref 27. Tagliavini F, Ghiso J, Timmers W, Giaccone G, Bulgiani O, Frangione B. Coexistence of Alzheimer's amyloid precursor protein and amyloid protein in cerebral vessel walls . Lab Invest . 1990;62:761-767. 28. Seubert P, Vigo-Pelfrey C, Esch F, et al. Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids . Nature . 1992;359:325-327.Crossref 29. Arai H, Lee VM-Y, Messinger ML, Greenberg BD, Lowery DE, Trojanowski JQ. Expression patterns of β-amyloid precursor protein (β-APP) in neural and nonneural human tissues from Alzheimer's disease and control subjects . Ann Neurol . 1991;30:686-693.Crossref 30. Rumble B, Retallack R, Hilbich C, et al. Amyloid A4 protein and its precursor in Down's syndrome and Alzheimer's disease . N Engl J Med . 1989;320:1446-1452.Crossref 31. Perlmutter LS, Chang Chui H. Microangiopathy, the vascular basement membrane and Alzheimer's disease: a review . Brain Res Bull . 1990;24:677-686.Crossref 32. Scheibel AB, Duong T, Tomiyasu U. Denervation microangiopathy in senile dementia, Alzheimer type . Alzheimer Dis Assoc Disord . 1987;1:19-37.Crossref 33. Katzman R, Saitoh T. Advances in Alzheimer's disease . FASEBJ . 1991;5:278-286. 34. Abe K, Tanzi RE, Kogure K. Selective induction of Kunitz-type protease inhibitor domain-containing amyloid precursor protein mRNA after persistent focal ischemia in rat cerebral cortex . Neurosci Lett . 1991;125:172-174.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Neurology American Medical Association

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

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References (42)

Publisher
American Medical Association
Copyright
Copyright © 1994 American Medical Association. All Rights Reserved.
ISSN
0003-9942
eISSN
1538-3687
DOI
10.1001/archneur.1994.00540200075019
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Abstract

Abstract Objectives: As a possible diagnostic marker for Alzheimer's disease (AD), we investigated β-amyloid protein (β/A4) immunoreactivity in skin. Furthermore, we studied the presence of β-amyloid precursor protein 695 immunoreactivity in skin. Design: Lifetime skin biopsy specimens were stained for β/A4 and β-amyloid precursor protein 695. The follow-up period was 12 months. We determined the correlation between β/A4 immunoreactivity in skin and brain in patients with a neuropathologic diagnosis. Setting: All patients with dementia were hospitalized; most of them had moderate to severe dementia. Aged nondemented controls were residents of a nursing home. The Down's syndrome (DS) group included both hospitalized and ambulatory patients. Young nondemented controls were medical students or staff members who volunteered for the study. Patients and Other Participants: The study included a total of 111 subjects. Thirty-five patients had probable AD, nine had possible AD, 15 had multiinfarct dementia, one had idiopathic Parkinson's disease, and one had Parkinson's disease and possible AD. There were also 19 elderly nondemented controls, 23 patients with DS, and eight young nondemented controls. Main Outcome Measures: Immunohistochemical detection of β/A4 in skin and correlation to the diagnosis of AD. Results: Immunopositivity for β/A4 antibody was present in and around the endothelium of dermal blood vessels in a proportion of patients with AD and multi-infarct dementia as well as elderly controls. The patients with sporadic AD displayed β/A4 immunoreactivity significantly more frequently than did patients with familial AD, patients with multi-infarct dementia, and controls. The β/A4 immunopositivity in skin was rare in the patients with DS and not present in young controls. Instead, 48% of patients with DS but none of other groups had β-amyloid precursor protein 695 immunoreactivity in skin. Only four (31%) of 13 patients with neuropathologically confirmed AD had shown endothelial β/A4 immunopositivity in skin biopsy specimens while alive. Conclusion: Our results do not support β/A4 as a diagnostic marker for AD. References 1. Goedert M. Neuronal localization of amyloid beta protein precursor mRNA in normal human brain and in Alzheimer's disease . EMBO J . 1987;235:3627-3632. 2. Kang J, Lemaire H-G, Unterbeck A, et al. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor . Nature . 1987;325:733-736.Crossref 3. Oltersdorf T, Friz LC, Schenk DB. The secreted form of Alzheimer amyloid precursor protein with the Kunitz domain is protease nexin-II . Nature . 1989:341: 144-147. 4. Glenner GG. Alzheimer's disease: its proteins and genes . Cell . 1988;52:307-308.Crossref 5. Müller-Hill B, Beyreuther K. Molecular biology of Alzheimer's disease . Annu Rev Biochem . 1989;58:287-307.Crossref 6. Tanzi RE, Gusella JF, Watkins PC, et al. Amyloid β protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus . Science . 1987;235: 860-864.Crossref 7. Palmert MR, Usiak M, Mayeux R, Raskind M, Tourtellotte WW, Younkin SG. Soluble derivatives of the β amyloid protein precursor in cerebrospinal fluid: alterations in normal aging and in Alzheimer's disease . Neurology . 1990;40: 1028-1034.Crossref 8. Podlisny MB, Mammen AL, Schlossmacher MG, Palmert MR, Younkin SG, Selkoe DJ. Detection of soluble forms of the β-amyloid precursor protein in human plasma . Biochem Biophys Res Commun . 1990;167:1094-1101.Crossref 9. Joachim C, Mori H, Selkoe D. Amyloid beta-protein deposition in tissues other than brain in Alzheimer's disease . Nature . 1989;341:226-230.Crossref 10. Soininen H, Syrjänen S, Heinonen O, et al. Amyloid-β-protein deposition in skin of patients with dementia . Lancet . 1992;339:245.Crossref 11. Mann DMA. The pathological association between Down syndrome and Alzheimer's disease . Mech Ageing Dev . 1988;43:99-136.Crossref 12. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. 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 . 1984;34:939-944.Crossref 13. American Psychiatric Association, Committee on Nomenclature and Statistics. Diagnostic and Statistical Manual of Mental Disorders , Third Edition. Washington, DC: American Psychiatric Association; 1980. 14. Folstein MF, Folstein SE, McHugh PR. Mini-Mental State: a practical method for grading cognitive state of patients for the clinician . J Psychiatr Res . 1975; 12:189-198.Crossref 15. Blessed G, Tomlinson BE, Roth M. The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects . Br J Psychiatry . 1968;114:797-811.Crossref 16. Rosen WG, Terry RD, Fuld PA, Katzman R, Peck A. Pathological verification of ischemic score in differentiation of dementias . Ann Neurol . 1980;7:486-488.Crossref 17. Mirra SS, Heyman A, McKeel D, et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD), II: standardization of the neuropathologic assessment of Alzheimer's disease . Neurology . 1991;41:479-486.Crossref 18. Bielschowsky M. Die Silberimpragnation der Axenzylinder . Centralplatt Neurol . 1902;22:579. 19. Bennhold H. Eine spesifische Amyloidfärbung mit Kangorot . Munch Med Wochenschr . 1922;33:1537. 20. Perry RH, Irving D, Blessed G, Fairbairn A, Perry E. Senile dementia of Lewy body type: a clinically and neuropathologically distinct form of Lewy body dementia in the elderly . J Neurol Sci . 1990;95:119-139.Crossref 21. Ikeda M, Shoji M, Yamaguchi H, et al. Diagnostic significance of skin immunolabelling with antibody against native cerebral amyloid in Alzheimer's disease . Neurosci Lett . 1993;150:159-161.Crossref 22. Haass C, Hung A, Selkoe D. Processing of β-amyloid precursor protein in micorglia and astrocytes favors an internal localization over constitutive secretion . J Neurosci . 1991;11:3783-3793. 23. Neve R, Finch E, Dawes L. Expression of the Alzheimer amyloid precursor gene transcripts in the human brain . Neuron . 1988;1:669-677.Crossref 24. Schmechel D, Goldgaber D, Burkhart D, Gilbert J, Gajdusek D, Roses A. Cellular localization of messenger RNA encoding amyloid-beta-protein in normal tissue and in Alzheimer's disease . Alzheimer Dis Assoc Disord . 1988;2:96-111.Crossref 25. Bush Al, Martins RN, Rumble B. The amyloid precursor protein of Alzheimer's disease is released by human platelets . J Biol Chem . 1990;265:15977-15983. 26. Schlossmacher MG, Ostaszewski BL, Hecker LI. Detection of distinct isoform patterns of the β-amyloid precursor protein in human platelets and lymphocytes . Neurobiol Aging . 1992;13:421-434.Crossref 27. Tagliavini F, Ghiso J, Timmers W, Giaccone G, Bulgiani O, Frangione B. Coexistence of Alzheimer's amyloid precursor protein and amyloid protein in cerebral vessel walls . Lab Invest . 1990;62:761-767. 28. Seubert P, Vigo-Pelfrey C, Esch F, et al. Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids . Nature . 1992;359:325-327.Crossref 29. Arai H, Lee VM-Y, Messinger ML, Greenberg BD, Lowery DE, Trojanowski JQ. Expression patterns of β-amyloid precursor protein (β-APP) in neural and nonneural human tissues from Alzheimer's disease and control subjects . Ann Neurol . 1991;30:686-693.Crossref 30. Rumble B, Retallack R, Hilbich C, et al. Amyloid A4 protein and its precursor in Down's syndrome and Alzheimer's disease . N Engl J Med . 1989;320:1446-1452.Crossref 31. Perlmutter LS, Chang Chui H. Microangiopathy, the vascular basement membrane and Alzheimer's disease: a review . Brain Res Bull . 1990;24:677-686.Crossref 32. Scheibel AB, Duong T, Tomiyasu U. Denervation microangiopathy in senile dementia, Alzheimer type . Alzheimer Dis Assoc Disord . 1987;1:19-37.Crossref 33. Katzman R, Saitoh T. Advances in Alzheimer's disease . FASEBJ . 1991;5:278-286. 34. Abe K, Tanzi RE, Kogure K. Selective induction of Kunitz-type protease inhibitor domain-containing amyloid precursor protein mRNA after persistent focal ischemia in rat cerebral cortex . Neurosci Lett . 1991;125:172-174.Crossref

Journal

Archives of Neurology – American Medical Association

Published: Aug 1, 1994

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