Analysis of the Cerebrospinal Fluid Proteome in Alzheimer's Disease

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Emami Khoonsari, PayamUppsala universitet,Cancerfarmakologi och beräkningsmedicin (author)

Analysis of the Cerebrospinal Fluid Proteome in Alzheimer's Disease

Article/chapterEnglish2016

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2016-03-07
Public Library of Science (PLoS),2016
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LIBRIS-ID:oai:DiVA.org:kth-185066
https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-185066URI
https://doi.org/10.1371/journal.pone.0150672DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-283774URI

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Language:English
Summary in:English

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QC 20160415
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.

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Häggmark, AnnaKTH,Proteomik och nanobioteknologi,Science for Life Laboratory, SciLifeLab,Affinity Proteomics,KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, Sci Life Lab, Stockholm, Sweden.(Swepub:kth)u1g5roxd (author)
Lönnberg, MariaUppsala universitet,Analytisk kemi(Swepub:uu)malon498 (author)
Mikus, MariaKTH,Proteomik och nanobioteknologi,Science for Life Laboratory, SciLifeLab,Affinity Proteomics,KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, Sci Life Lab, Stockholm, Sweden.(Swepub:kth)u1qjoszn (author)
Kilander, LenaUppsala universitet,Geriatrik(Swepub:uu)lekil226 (author)
Lannfelt, LarsUppsala universitet,Geriatrik(Swepub:uu)lalan021 (author)
Bergquist, JonasUppsala universitet,Analytisk kemi(Swepub:uu)jbe25356 (author)
Ingelsson, MartinUppsala universitet,Geriatrik(Swepub:uu)maing121 (author)
Nilsson, PeterKTH,Proteomik och nanobioteknologi,Science for Life Laboratory, SciLifeLab,Affinity Proteomics,KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, Sci Life Lab, Stockholm, Sweden.(Swepub:kth)u1ws88sk (author)
Kultima, KimUppsala universitet,Cancerfarmakologi och beräkningsmedicin(Swepub:uu)kikul535 (author)
Shevchenko, GannaUppsala universitet,Analytisk kemi,Uppsala Univ, Dept Chem BMC, Analyt Chem, Uppsala, Sweden.(Swepub:uu)gansc354 (author)
Uppsala universitetCancerfarmakologi och beräkningsmedicin (creator_code:org_t)

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In:PLOS ONE: Public Library of Science (PLoS)11:31932-6203

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