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- Brinkmalm, Gunnar, et al.
(författare)
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Soluble amyloid precursor protein alpha and beta in CSF in Alzheimer's disease
- 2013
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Ingår i: Brain Research. - : Elsevier BV. - 1872-6240 .- 0006-8993. ; 1513, s. 117-126
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 2. |
- Nutu, Magdalena, et al.
(författare)
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Evaluation of the Cerebrospinal Fluid Amyloid-beta(1-42)/Amyloid-beta(1-40) Ratio Measured by Alpha-LISA to Distinguish Alzheimer's Disease from Other Dementia Disorders
- 2013
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 36:1-2, s. 99-110
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Tidskriftsartikel (refereegranskat)abstract
- Background: The well-established core biomarkers used to identify Alzheimer's disease (AD) overlap with other dementia disorders such as dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD). This study aimed to evaluate whether the cerebrospinal fluid (CSF) amyloid-beta (A beta)(1-42)/A beta(1-40) ratio, measured by a novel method, could improve the differential diagnosis of AD, DLB and PDD. Method: CSF levels of A beta(1-40) and A beta(1-42) in patients with PDD, DLB, AD, Parkinson's disease and controls were analyzed using an amplified luminescent proximity homogenous immunoassay along with conventional immunoassays. Results: The CSF A beta(1-42)/A beta(1-40) ratio increased discrimination of AD from PDD and DLB compared with either of the two A beta biomarkers individually. Conclusion: The use of the A beta(1-42)/A beta(1-40) ratio could improve the differentiation of AD from PDD and DLB. (C) 2013 S. Karger AG, Basel
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