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
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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