Identification of novel N-terminal fragments of amyloid precursor protein in cerebrospinal fluid

被引：36

作者：

Portelius, Erik ^{[1
]}

Brinkmalm, Gunnar ^{[1
]}

Tran, AiJun ^{[1
]}

Andreasson, Ulf ^{[1
]}

Zetterberg, Henrik ^{[1
]}

Westman-Brinkmalm, Ann ^{[1
]}

Blennow, Kaj ^{[1
]}

Ohrfelt, Annika ^{[1
]}

机构：

[1] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, S-43180 Molndal, Sweden

来源：

EXPERIMENTAL NEUROLOGY | 2010年 / 223卷 / 02期

基金：

瑞典研究理事会;

关键词：

Alzheimer's disease; Amyloid precursor protein; Cerebrospinal fluid; Immunoprecipitation; Mass spectrometry; ALZHEIMERS-DISEASE; BETA-PROTEIN; BINDING DOMAIN; CELL; TAU; LOCALIZATION;

D O I：

10.1016/j.expneurol.2009.06.011

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the central nervous system. Two pathological hallmarks in the brain of AD patients are neurofibrillary tangles and senile plaques. The plaques consist mainly of beta-amyloid (A beta) peptides that are produced from the amyloid precursor protein (APP), by sequential cleavage by beta- and gamma-secretase. Most previous studies have been focused on the C-terminal fragments of APP, where the A beta sequence is localized. The purpose of this study was to search for N-terminal fragments of APP in cerebrospinal fluid (CSF) using mass spectrometry (MS). By using immunoprecipitation (IP) combined with matrix-assisted laser desorption/ionization time-of-flight MS as well as nanoflow liquid chromatography coupled to high resolution tandem MS we were able to detect and identify six novel N-terminal APP fragments [APP((18-119)), APP((18-121)), APP((18-122)), APP((18-123)), APP((18-124)) and APP((18-126))], having molecular masses of approximately 12 kDa. The presence of these APP derivatives in CSF was also verified by Western blot analysis. Two pilot studies using either IP-MS or Western blot analysis indicated slightly elevated levels of N-terminal APP fragments in CSF from AD patients compared with controls, which are in need of replications in independent and larger patient materials. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：351 / 358

页数：8

共 33 条

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