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皮肤中β-淀粉样蛋白免疫反应性并非阿尔茨海默病的可靠标志物。一项尸检对照研究。

beta-Amyloid protein immunoreactivity in skin is not a reliable marker of Alzheimer's disease. An autopsy-controlled study.

作者信息

Heinonen O, Soininen H, Syrjänen S, Neittaanmäki H, Paljärvi L, Kosunen O, Syrjänen K, Riekkinen P

机构信息

Department of Neurology, University of Kuopio, Findland.

出版信息

Arch Neurol. 1994 Aug;51(8):799-804. doi: 10.1001/archneur.1994.00540200075019.

DOI:10.1001/archneur.1994.00540200075019
PMID:8042928
Abstract

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.

摘要

目的

作为阿尔茨海默病(AD)的一种可能诊断标志物,我们研究了皮肤中β-淀粉样蛋白(β/A4)的免疫反应性。此外,我们还研究了皮肤中β-淀粉样前体蛋白695免疫反应性的存在情况。

设计

对终生皮肤活检标本进行β/A4和β-淀粉样前体蛋白695染色。随访期为12个月。我们确定了神经病理学诊断患者皮肤和大脑中β/A4免疫反应性之间的相关性。

背景

所有痴呆患者均住院治疗;他们大多数患有中度至重度痴呆。老年非痴呆对照组为养老院居民。唐氏综合征(DS)组包括住院患者和非卧床患者。年轻非痴呆对照组为自愿参加该研究的医学生或工作人员。

患者及其他参与者

该研究共纳入111名受试者。35例患者可能患有AD,9例可能患有AD,15例患有多发性梗死性痴呆,1例患有特发性帕金森病,1例患有帕金森病且可能患有AD。此外,还有19名老年非痴呆对照组、23例DS患者和8名年轻非痴呆对照组。

主要观察指标

皮肤中β/A4的免疫组织化学检测及其与AD诊断的相关性。

结果

在部分AD、多发性梗死性痴呆患者以及老年对照组的真皮血管内皮及其周围存在β/A4抗体免疫阳性。散发性AD患者出现β/A4免疫反应性的频率显著高于家族性AD患者、多发性梗死性痴呆患者及对照组。DS患者皮肤中β/A4免疫阳性罕见,年轻对照组中则不存在。相反,48%的DS患者皮肤中有β-淀粉样前体蛋白695免疫反应性,而其他组均无。13例经神经病理学证实为AD的患者中,只有4例(31%)在生前皮肤活检标本中显示内皮β/A4免疫阳性。

结论

我们的结果不支持β/A4作为AD的诊断标志物。

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