β淀粉样前体蛋白717位的阿尔茨海默病突变增加了以Aβ42（43）结尾的血浆淀粉样β蛋白的百分比。

The beta APP717 Alzheimer mutation increases the percentage of plasma amyloid-beta protein ending at A beta42(43).

作者信息

Kosaka T, Imagawa M, Seki K, Arai H, Sasaki H, Tsuji S, Asami-Odaka A, Fukushima T, Imai K, Iwatsubo T

机构信息

Department of Neuropathology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.

出版信息

Neurology. 1997 Mar;48(3):741-5. doi: 10.1212/wnl.48.3.741.

DOI:10.1212/wnl.48.3.741

PMID:9065558

Abstract

We measured plasma levels of amyloid beta protein (A beta) ending at positions 40 (A beta40) and 42(43) [A beta42(43)] in six carriers of beta APP717 (Val to Ile) mutation linked to familial Alzheimer's disease (FAD) as well as in patients with sporadic AD (sAD) and controls. The percentage and the level of A beta42(43) were significantly higher in carriers of beta APP717 mutation relative to sAD, whereas A beta40 levels were decreased. In contrast, A beta levels and ratios were at similar levels in sAD, regardless of the stage of the disease, compared with non-AD neurologic disease controls and nondemented control individuals. These results suggest that the reported increase in the percentage of A beta42(43) secretion in transfected cells with beta APP717 mutant genes actually takes place in the bodies of carriers of beta APP717 mutation, and that plasma A beta could be used as an indicator of the alterations of beta APP/A beta metabolism in subtypes of AD.

摘要

我们检测了与家族性阿尔茨海默病（FAD）相关的β-淀粉样前体蛋白（βAPP）717（缬氨酸至异亮氨酸）突变的6名携带者、散发性AD（sAD）患者以及对照者血浆中40位（Aβ40）和42（43）位（Aβ42（43））的淀粉样β蛋白（Aβ）水平。相对于sAD，βAPP717突变携带者中Aβ42（43）的百分比和水平显著更高，而Aβ40水平降低。相比之下，与非AD神经系统疾病对照者和非痴呆对照个体相比，sAD患者的Aβ水平和比率在疾病的各个阶段均处于相似水平。这些结果表明，在转染了βAPP717突变基因的细胞中，所报道的Aβ42（43）分泌百分比的增加实际上发生在βAPP717突变携带者体内，并且血浆Aβ可作为AD亚型中βAPP/Aβ代谢改变的指标。