BETA-AMYLOID PROTEIN IMMUNOREACTIVITY IN SKIN IS NOT A RELIABLE MARKER OF ALZHEIMERS-DISEASE - AN AUTOPSY-CONTROLLED STUDY

Objectives: As a possible diagnostic marker for Alzheimer's disease (A D), 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 spe cimens were stained for beta/A4 and beta-amyloid precursor protein 695 . The follow-up period was 12 months. We determined the correlation be tween beta/A4 immunoreactivity in skin and brain in patients with a ne uropathologic diagnosis. Setting: All patients with dementia were hosp italized; most of them had moderate to severe dementia. Aged nondement ed controls were residents of a nursing home. The Down's syndrome (DS) group included both hospitalized and ambulatory patients. Young nonde mented 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 Parkinso n's disease, and one had Parkinson's disease and possible AD. There we re also 19 elderly nondemented controls, 23 patients with DS, and eigh t young nondemented controls. Main Outcome Measures: Immunohistochemic al detec tion of beta/A4 in skin and correlation to the diagnosis of A D. Results: immunopositivity for beta/A4 antibody was present in and a round the endothelium of dermal blood vessels in a proportion of patie nts with AD and multi-infarct dementia as well as elderly controls. Th e patients with sporadic AD displayed beta/A4 immunoreactivity signifi cantly more frequently than did patients with familial AD, patients wi th multi-infarct dementia, and controls. The beta/A4 immunopositivity in skin was rare in the patients with DS and not present in young cont rols. Instead, 48% of patients with DS but none of other groups had be ta-amyloid precursor protein 695 immunoreactivity in skin. Only four ( 31%) of 13 patients with neuropathologically confirmed AD had shown en dothelial beta/A4 immunopositivity in skin biopsy specimens while aliv e. Conclusion: Our results do not support beta/A4 as a diagnostic mark er for AD.