DECREASED ALPHA-SECRETASE-CLEAVED AMYLOID PRECURSOR PROTEIN AS A DIAGNOSTIC MARKER FOR ALZHEIMERS-DISEASE

被引：145

作者：

LANNFELT, L ^{[1
]}

BASUN, H ^{[1
]}

WAHLUND, LO ^{[1
]}

ROWE, BA ^{[1
]}

WAGNER, SL ^{[1
]}

机构：

[1] SIBIA,LA JOLLA,CA 92037

来源：

NATURE MEDICINE | 1995年 / 1卷 / 08期

关键词：

D O I：

10.1038/nm0895-829

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

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页码：829 / 832

页数：4

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