Analysis of the Cerebrospinal Fluid Proteome in Alzheimer's Disease.
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 re...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4780771?pdf=render |
| _version_ | 1819035174824837120 |
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| author | Payam Emami Khoonsari Anna Häggmark Maria Lönnberg Maria Mikus Lena Kilander Lars Lannfelt Jonas Bergquist Martin Ingelsson Peter Nilsson Kim Kultima Ganna Shevchenko |
| author_facet | Payam Emami Khoonsari Anna Häggmark Maria Lönnberg Maria Mikus Lena Kilander Lars Lannfelt Jonas Bergquist Martin Ingelsson Peter Nilsson Kim Kultima Ganna Shevchenko |
| author_sort | Payam Emami Khoonsari |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T07:45:26Z |
| format | Article |
| id | doaj.art-c3e197b8544d4f78965d0847c37e165d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T07:45:26Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c3e197b8544d4f78965d0847c37e165d2022-12-21T19:11:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01113e015067210.1371/journal.pone.0150672Analysis of the Cerebrospinal Fluid Proteome in Alzheimer's Disease.Payam Emami KhoonsariAnna HäggmarkMaria LönnbergMaria MikusLena KilanderLars LannfeltJonas BergquistMartin IngelssonPeter NilssonKim KultimaGanna ShevchenkoAlzheimer'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.http://europepmc.org/articles/PMC4780771?pdf=render |
| spellingShingle | Payam Emami Khoonsari Anna Häggmark Maria Lönnberg Maria Mikus Lena Kilander Lars Lannfelt Jonas Bergquist Martin Ingelsson Peter Nilsson Kim Kultima Ganna Shevchenko Analysis of the Cerebrospinal Fluid Proteome in Alzheimer's Disease. PLoS ONE |
| title | Analysis of the Cerebrospinal Fluid Proteome in Alzheimer's Disease. |
| title_full | Analysis of the Cerebrospinal Fluid Proteome in Alzheimer's Disease. |
| title_fullStr | Analysis of the Cerebrospinal Fluid Proteome in Alzheimer's Disease. |
| title_full_unstemmed | Analysis of the Cerebrospinal Fluid Proteome in Alzheimer's Disease. |
| title_short | Analysis of the Cerebrospinal Fluid Proteome in Alzheimer's Disease. |
| title_sort | analysis of the cerebrospinal fluid proteome in alzheimer s disease |
| url | http://europepmc.org/articles/PMC4780771?pdf=render |
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