期刊
BRAIN RESEARCH
卷 1513, 期 -, 页码 117-126出版社
ELSEVIER
DOI: 10.1016/j.brainres.2013.03.019
关键词
AlphaLISA immunoassay; Immunoprecipitation; Mass spectrometry; Cerebrospinal fluid; Soluble amyloid precursor protein (sAPP)
资金
- Swedish Research Council [8266, 14002, K2010-63P-21562-01-4, K2011-61X-20401-05-6]
- BIOMARICAPD Project
- cNEUPRO (EC) [LSHM-CT-2007-037950]
- Sahlgrenska University Hospital, Demensfonden, Stiftelsen Gamla Tjanarinnor
- IngaBritt and Arne Lundberg Research Foundation
- Soderberg Foundation
- Eivind and Elsa K:son Sylvans Stiftelse
- Goteborg Medical Society
- Swedish Brain Power
- Magn. Bergvall Foundation
- Gun and Bertil Stohne Foundation
- Torsten and Ragnar Soderberg Foundation
- Thureus Foundation
- Stiftelsen Psykiatriska Forskningsfonden, Uppsala Universitet (Medicinska Fakultetens Stiftelse for Psykiatrisk och Neurologisk Forskning)
- Alzheimer Foundation, Sweden
Objective: Cerebral accumulation of amyloid beta (A beta) is a pathological hallmark of Alzheimer's disease (AD). Proteolytic processing of amyloid precursor protein (APP) by alpha- or beta-secretase results in two soluble metabolites, sAPP alpha and sAPP beta, respectively. However, previous data have shown that both alpha- and beta-secretase have multiple cleavage sites. The aim of this study was to characterize the C-termini of sAPP alpha and sAPP beta in cerebrospinal fluid (CSF) by mass spectrometry (MS) and to evaluate whether different combinations of these fragments better separate between AD patients and controls by comparing two different sAPP immunoassays. Methods: Using immunoprecipitation and high resolution MS, the APP species present in CSF were investigated. CSF levels of sAPP alpha and sAPP beta from patients with AD (n=43) and from non-demented controls (n=44) were measured using AlphaLISA and MSD immunoassays that employ different antibodies for C-terminal recognition of sAPP alpha. Results: Four different C-terminal forms of sAPP were identified, sAPP beta-M671, sAPP beta-Y681, sAPP alpha-Q686, and 5APP alpha-K687 (APP770 numbering). Neither immunoassay for the sAPP species could separate the two patient groups. The correlation (R-2) between the two immunoassays was 0.41 for sAPP alpha and 0.45 for sAPP beta. Conclusion: Using high resolution MS, we show here for the first time that sAPP alpha in CSF ends at Q686 and K687. The findings also support the conclusion from several previous studies that sAPP alpha and sAPP beta levels are unaltered in AD. (C) 2013 Elsevier B.V. All rights reserved.
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