Lannfelt L, Basun H, Wahlund L O, Rowe B A, Wagner S L
Karolinska Institute, Department of Clinical Neuroscience (Geriatric Medicine), Huddinge University Hospital, Sweden.
Nat Med. 1995 Aug;1(8):829-32. doi: 10.1038/nm0895-829.
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 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 APP670/671 (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.
阿尔茨海默病（AD）的神经病理学特征是细胞外斑块和细胞内神经原纤维缠结。AD中老年斑的一个成分是β-淀粉样蛋白，它是一种由39 - 43个氨基酸组成的疏水肽，是淀粉样前体蛋白（APP）的一个片段。APP至少可通过两条途径代谢，其中一条途径涉及一种名为α-分泌酶的未知酶生成可溶性APP。这种切割产生α-分泌酶切割的可溶性APP（α-sAPP），在本研究中，通过一种新的检测方法对来自一个瑞典AD家族成员的脑脊液（CSF）中的α-sAPP进行了测量，该家族在APP670/671位点存在致病突变（参考文献2）。携带该突变并被诊断为AD的家族成员α-sAPP水平较低（160±48 ng/ml），与非携带者（257±48 ng/ml）相比无重叠。症状前突变携带者的α-sAPP水平处于中间值。目前AD尚无具有足够敏感性和特异性的生前诊断标志物，但α-sAPP的测量代表了一种新的、有前景的诊断标志物。
