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Analysis of the Cerebrospinal Fluid Proteome in Alzheimer's Disease
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, Sci Life Lab, Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, Sci Life Lab, Stockholm, Sweden..
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 3, e0150672Article in journal (Refereed) PublishedText
Abstract [en]

Alzheimer's disease is a neurodegenerative disorder accounting for more than 50% of cases of dementia. Diagnosis of Alzheimer's disease relies on cognitive tests and analysis of amyloid beta, protein tau, and hyperphosphorylated tau in cerebrospinal fluid. Although these markers provide relatively high sensitivity and specificity for early disease detection, they are not suitable for monitor of disease progression. In the present study, we used label-free shotgun mass spectrometry to analyse the cerebrospinal fluid proteome of Alzheimer's disease patients and non-demented controls to identify potential biomarkers for Alzheimer's disease. We processed the data using five programs (DecyderMS, Maxquant, OpenMS, PEAKS, and Sieve) and compared their results by means of reproducibility and peptide identification, including three different normalization methods. After depletion of high abundant proteins we found that Alzheimer's disease patients had lower fraction of low-abundance proteins in cerebrospinal fluid compared to healthy controls (p<0.05). Consequently, global normalization was found to be less accurate compared to using spiked-in chicken ovalbumin for normalization. In addition, we determined that Sieve and OpenMS resulted in the highest reproducibility and PEAKS was the programs with the highest identification performance. Finally, we successfully verified significantly lower levels (p<0.05) of eight proteins (A2GL, APOM, C1QB, C1QC, C1S, FBLN3, PTPRZ, and SEZ6) in Alzheimer's disease compared to controls using an antibody-based detection method. These proteins are involved in different biological roles spanning from cell adhesion and migration, to regulation of the synapse and the immune system.

Place, publisher, year, edition, pages
2016. Vol. 11, no 3, e0150672
National Category
Neurology Geriatrics
URN: urn:nbn:se:uu:diva-283774DOI: 10.1371/journal.pone.0150672ISI: 000371990100049PubMedID: 26950848OAI: oai:DiVA.org:uu-283774DiVA: diva2:919656
Knut and Alice Wallenberg FoundationMarianne and Marcus Wallenberg FoundationThe Swedish Brain FoundationSwedish Research Council FormasSwedish Research Council, P29797-1Swedish Research Council, 621-2011-4423
Available from: 2016-04-14 Created: 2016-04-14 Last updated: 2016-04-14Bibliographically approved

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Lönnberg, MariaKilander, LenaLannfelt, LarsBergquist, JonasIngelsson, MartinKultima, KimShevchenko, Ganna
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