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An Autopsy-Controlled Study

Outi Heinonen, MSc; Hilkka Soininen, MD, PhD; Stina Syrjänen, DDS, PhD; Heikki Neittaanmäki, MD, PhD; Leo Paljärvi, MD, PhD; Olli Kosunen, MD; Kari Syrjänen, MD, PhD; Paavo Riekkinen, Sr, MD, PhD

Arch Neurol. 1994;51(8):799-804.

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.

Author Affiliations
From the Departments of Neurology (Ms Heinonen and Drs Soininen and Riekkinen), Pathology (Drs S. Syrjänen, Paljärvi, Kosunen, and K. Syrjänen), and Dermatology (Dr Neittaanmäki) and the A. I. Virtanen Institute (Dr Riekkinen), University of Kuopio (Finland).

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