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The amyloid-beta degradation pattern in plasma A possible tool for clinical trials in Alzheimer's disease
Univ Gothenburg, Sahlgrenska Acad, Dept Psychiat & Neurochem, Inst Neurosci & Physiol, Gothenburg, Sweden.
Univ Gothenburg, Sahlgrenska Acad, Dept Psychiat & Neurochem, Inst Neurosci & Physiol, Gothenburg, Sweden.
Univ Gothenburg, Sahlgrenska Acad, Dept Psychiat & Neurochem, Inst Neurosci & Physiol, Gothenburg, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
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2014 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 573, p. 7-12Article in journal (Refereed) Published
Abstract [en]

Amyloid beta (A beta) is the main component of plaques, the central neuropathological hallmark in Alzheimer's disease (AD). A beta is derived from the amyloid precursor protein (APP) by beta- and gamma-secretase-mediated cleavages. A large number of A beta peptides are found in cerebrospinal fluid and these peptides are produced in specific metabolic pathways, which are important for diagnosis, in drug development and to explore disease pathogenesis. To investigate whether a similar pattern could be found also in blood samples, an immunoprecipitation (IP) based method for enrichment of A beta peptides from human plasma was developed. The peptides were analyzed using matrix-assisted-laser-desorption/ionization time-of-flight/time-of-flight mass spectrometry for A beta profiling and selected reaction monitoring (SRM) for MS quantification of A beta 1-38, A beta 1-40 and A beta 1-42 using tripe quadrupole MS. Sixteen N- or C-terminally truncated A beta peptides were reproducibly detected in human plasma, of which 11 were verified by tandem MS. In a pilot study including 9 AD patients and 10 controls, where A beta 1-38, A beta 1-40 and A beta 1-42 were quantified using SRM, no AD-associated change in plasma levels of the peptides were observed. Using MS-based measurement techniques, we show that several A beta peptides can be monitored in a single analysis and the developed methods have the potential to be used as a read out in clinical trials of drugs affecting APP processing or A beta homeostasis.  

Place, publisher, year, edition, pages
2014. Vol. 573, p. 7-12
Keywords [en]
Plasma, Alzheimer's disease, Mass spectrometry, Amyloid beta, Immunoprecipitation
National Category
Geriatrics
Identifiers
URN: urn:nbn:se:uu:diva-229520DOI: 10.1016/j.neulet.2014.04.041ISI: 000338399700002PubMedID: 24796810OAI: oai:DiVA.org:uu-229520DiVA, id: diva2:737199
Funder
Swedish Research Council Formas, 14002 K2010-63P-21562-01-4 K2011-61X-20401-05-6Stiftelsen Gamla TjänarinnorMagnus Bergvall FoundationKnut and Alice Wallenberg FoundationThe Swedish Brain FoundationThe Dementia Association - The National Association for the Rights of the DementedWenner-Gren Foundations
Note

Correction in: Neuroscience Letters, vol. 599, pages 67-68, DOI: 10.1016/j.neulet.2015.05.042

Available from: 2014-08-12 Created: 2014-08-11 Last updated: 2017-12-05Bibliographically approved

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Ingelsson, MartinLannfelt, Lars

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