beta-Amyloid protein immunoreactivity in skin is not a reliable marker of Alzheimer's disease. An autopsy-controlled study
O. Heinonen, H. Soininen, S. Syrjanen, H. Neittaanmaki, L. Paljarvi, O. Kosunen, K. Syrjanen and Sr. Riekkinen P
Department of Neurology, University of Kuopio, Findland.
OBJECTIVES: As a possible diagnostic marker for Alzheimer's disease (AD),
we investigated beta-amyloid protein (beta/A4) immunoreactivity in skin.
Furthermore, we studied the presence of beta-amyloid precursor protein 695
immunoreactivity in skin. DESIGN: Lifetime skin biopsy specimens were
stained for beta/A4 and beta-amyloid precursor protein 695. The follow-up
period was 12 months. We determined the correlation between beta/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
multi-infarct 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 beta/A4 in skin and
correlation to the diagnosis of AD. RESULTS: Immunopositivity for beta/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 beta/A4
immunoreactivity significantly more frequently than did patients with
familial AD, patients with multi-infarct dementia, and controls. The
beta/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 beta-amyloid precursor protein 695 immunoreactivity in
skin. Only four (31%) of 13 patients with neuropathologically confirmed AD
had shown endothelial beta/A4 immunopositivity in skin biopsy specimens
while alive. CONCLUSION: Our results do not support beta/A4 as a diagnostic
marker for AD.
