Analysis of the Cerebrospinal Fluid Proteome in Alzheimers Disease

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Published: 2016-03-08

Formatted citation

Khoonsari PE, Häggmark A, Lönnberg M, Mikus M, Kilander L, Lannfelt L, Bergquist J, Ingelsson M, Nilsson P, Kultima K, Shevchenko G.. Analysis of the Cerebrospinal Fluid Proteome in Alzheimers Disease.
PLoS One. (2016). DOI: 10.1371/journal.pone.0150672

Abstract

Alzheimers disease is a neurodegenerative disorder accounting for more than 50% of cases of dementia. Diagnosis of Alzheimers 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 Alzheimers disease patients and non-demented controls to identify potential biomarkers for Alzheimers 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 Alzheimers 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 Alzheimers 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.