期刊
EXPERIMENTAL NEUROLOGY
卷 223, 期 2, 页码 351-358出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2009.06.011
关键词
Alzheimer's disease; Amyloid precursor protein; Cerebrospinal fluid; Immunoprecipitation; Mass spectrometry
资金
- Swedish Research Council [2006-6227, 2006-2740]
- Alzheimer's Association [NIRG-08-90356]
- cNEUPRO
- Sahlgrenska University Hospital
- Inga-Britt
- Arne Lundberg Research Foundation
- Goteborg Medical Society
- Swedish Brain Power
- Stiftelsen Gamla Tjanarinnor
- Ake Wiberg Foundation
- Gun och Bertil Stohnes Stiftelse
- Alzheimer Foundation, Sweden
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.
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