The 28-amino acid form of an APLP1-derived Abeta-like peptide is a surrogate marker for Abeta42 production in the central nervous system.
The 28-amino acid form of an APLP1-derived Abeta-like peptide is a surrogate marker for Abeta42 production in the central nervous system.
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DOI：
10.1002/emmm.200900026
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发表时间：
2009-07
影响因子：
11.1
通讯作者：
Takeda, Masatoshi
中科院分区：
文献类型：
--
作者：
Yanagida, Kanta;Okochi, Masayasu;Tagami, Shinji;Nakayama, Taisuke;Kodama, Takashi S.;Nishitomi, Kouhei;Jiang, Jingwei;Mori, Kohji;Tatsumi, Shin-ichi;Arai, Tetsuaki;Ikeuchi, Takeshi;Kasuga, Kensaku;Tokuda, Takahiko;Kondo, Masaki;Ikeda, Masaki;Deguchi, Kentaro;Kazui, Hiroaki;Tanaka, Toshihisa;Morihara, Takashi;Hashimoto, Ryota;Kudo, Takashi;Steiner, Harald;Haass, Christian;Tsuchiya, Kuniaki;Akiyama, Haruhiko;Kuwano, Ryozo;Takeda, Masatoshi
阿尔茨海默病（AD）相关的42-氨基酸形式的淀粉样蛋白-β（Aβ42）的替代标志物一直在寻找，因为它们可能有助于AD的诊断和疾病发病机制的阐明。在这里，我们证明了人脑脊液（CSF）中含有三种APLP 1衍生的Aβ样肽（APL 1 β），它们是由β和γ裂解产生的，浓度约为4.5 nM。APL 1 β25、APL 1 β27和APL 1 β28在AD脑中没有沉积。有趣的是，大多数γ-分泌酶调节剂（GSMs）和家族性AD相关早老素1突变体上调Aβ42的相对产量，导致培养细胞中APL 1 β28产量的平行增加。此外，在早老素1基因病理性突变患者的CSF中，APL 1 β28的相对水平高于非AD对照，而Aβ42的相对水平不变或较低。最引人注目的是，散发性AD患者（无论他们是否处于轻度认知障碍或AD阶段）的CSF中的相对APL 1 β28水平高于非AD对照。基于这些结果，我们建议将CSF中APL 1 β28的相对水平作为脑中Aβ42产生相对水平的候选替代标志物。
Surrogate markers for the Alzheimer disease (AD)-associated 42-amino acid form of amyloid-β (Aβ42) have been sought because they may aid in the diagnosis of AD and for clarification of disease pathogenesis. Here, we demonstrate that human cerebrospinal fluid (CSF) contains three APLP1-derived Aβ-like peptides (APL1β) that are generated by β- and γ-cleavages at a concentration of ∼4.5 nM. These novel peptides, APL1β25, APL1β27 and APL1β28, were not deposited in AD brains. Interestingly, most γ-secretase modulators (GSMs) and familial AD-associated presenilin1 mutants that up-regulate the relative production of Aβ42 cause a parallel increase in the production of APL1β28 in cultured cells. Moreover, in CSF from patients with pathological mutations in presenilin1 gene, the relative APL1β28 levels are higher than in non-AD controls, while the relative Aβ42 levels are unchanged or lower. Most strikingly, the relative APL1β28 levels are higher in CSF from sporadic AD patients (regardless of whether they are at mild cognitive impairment or AD stage), than those of non-AD controls. Based on these results, we propose the relative level of APL1β28 in the CSF as a candidate surrogate marker for the relative level of Aβ42 production in the brain.
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影响因子：
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