DECREASED ALPHA-SECRETASE-CLEAVED AMYLOID PRECURSOR PROTEIN AS A DIAGNOSTIC MARKER FOR ALZHEIMERS-DISEASE
DECREASED ALPHA-SECRETASE-CLEAVED AMYLOID PRECURSOR PROTEIN AS A DIAGNOSTIC MARKER FOR ALZHEIMERS-DISEASE
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DOI：
10.1038/nm0895-829
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发表时间：
1995-08-01
期刊：
影响因子：
82.9
通讯作者：
WAGNER, SL
中科院分区：
文献类型：
--
作者：
LANNFELT, L;BASUN, H;WAGNER, SL
阿尔茨海默病(AD)的神经病理特征是细胞外斑块和细胞内神经原纤维缠结。阿尔茨海默病老年斑的一个成分是β-淀粉样蛋白，一种39-43个氨基酸的疏水肽(1)和淀粉样前体蛋白(APP)的一段。APP可通过至少两条途径代谢，其中一条途径涉及一种名为α-分泌酶的未知酶产生可溶性APP。这种裂解产生α-分泌酶裂解的可溶性APP(α-SAPP)，在本研究中，通过一种新的检测方法在脑脊液(CSF)中检测到APP(670/671)致病突变的瑞典AD家族成员的APP(参考文献。2)。携带突变并被诊断为AD的家族成员的α-Sapp水平较低(160+/-48ngml(-1))，与非携带者(257+/-48ngml(-1))相比没有重叠。症状前突变的携带者显示出中等水平的α-Sapp。目前尚无足够灵敏度和特异度的AD生前标志物，但α-SAPP的测定代表了一种新的、有希望的诊断标志物。
The neuropathologic hallmarks of Alzheimer's disease (AD) are extracellular plaques and intracellular neurofibrillary tangles. A constituent of senile plaques in AD is beta-amyloid, a hydrophobic peptide of 39-43 amino acids(1) and a fragment of the amyloid precursor protein (APP). APP can be metabolized by at least two pathways, one of which involves generation of soluble APP by an unidentified enzyme named alpha-secretase. This cleavage generates alpha-secretase-cleaved, soluble APP (alpha-sAPP), which in this investigation was measured by a new assay in cerebrospinal fluid (CSF) from members of a Swedish AD family with a pathogenic mutation at APP(670/671) (ref. 2). Family members who carry the mutation and are diagnosed with AD had low levels of alpha-sAPP (160 +/- 48 ng ml(-1)), with no overlap compared with non-carriers (257 +/- 48 ng ml(-1)). Carriers of the presymptomatic mutation showed intermediate alpha-sAPP levels. Today there exists no antemortem marker in AD with sufficient sensitivity and specificity, but measurement of alpha-sAPP represents a new and promising diagnostic marker.