Proteome analysis of cerebrospinal fluid proteins in Alzheimer patients

Davidsson, Pia; Westman‐Brinkmalm, Ann; Nilsson, Carol L.; Lindbjer, Maria; Paulson, Linda; Andreasen, Niels; Sjögren, Magnus; Blennow, Kaj

doi:10.1097/00001756-200204160-00015

Cited by 186 publications

(148 citation statements)

References 20 publications

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“…Eleven of the 13 spots selected were found to represent eight different proteins (Table II) (see Supplemental Table 4S for peptide coverage maps). Interestingly four of these proteins have been shown to have altered levels in AD CSF, including ␣ 1 ␤-glycoprotein, prostaglandin D 2 synthase, cystatin C, and ␤ 2 -microglobulin (9,10,12). Consistent with previous studies, ␣ 1 ␤-glycoprotein is decreased in the CDR 0.5 group, whereas cystatin C and ␤ 2 -microglobulin are increased.…”

Section: Fig 3 Representative Gel Images and 3-d Representations Ofsupporting

confidence: 86%

“…Our results may clarify discrepancies among AD biomarker studies. Some studies have reported reduced levels of transthyretin in AD CSF (41)(42)(43)(44), whereas one study found no significant differences between AD and control groups (45), and one study has reported increased levels of transthyretin in the CSF of AD patients (9). A similar inconsistency was found with ubiquitin (increases (46 -48), no change (49), and decreases (9)).…”

Section: Fig 3 Representative Gel Images and 3-d Representations Ofmentioning

confidence: 93%

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Comparative Proteomic Analysis of Intra- and Interindividual Variation in Human Cerebrospinal Fluid

Malone

Fagan

et al. 2005

Molecular & Cellular Proteomics

114

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Cerebrospinal fluid (CSF) is a potential source of biomarkers for many disorders of the central nervous system, including Alzheimer disease (AD). Prior to comparing CSF samples between individuals to identify patterns of disease-associated proteins, it is important to examine variation within individuals over a short period of time so that one can better interpret potential changes in CSF between individuals as well as changes within a given individual over a longer time span. In this study, we analyzed 12 CSF samples, composed of pairs of samples from six individuals, obtained 2 weeks apart. Multiaffinity depletion, two-dimensional DIGE, and tandem mass spectrometry were used. A number of proteins whose abundance varied between the two time points was identified for each individual. Some of these proteins were commonly identified in multiple individuals. More importantly, despite the intraindividual variations, hierarchical clustering and multidimensional scaling analysis of the proteomic profiles revealed that two CSF samples from the same individual cluster the closest together and that the between-subject variability is much larger than the within-subject variability. Among the six subjects, comparison between the four cognitively normal and the two very mildly demented subjects also yielded some proteins that have been identified in previous AD biomarker studies. These results validate our method of identifying differences in proteomic profiles of CSF samples and have important implications for the design of CSF biomarker studies for AD and other central nervous system disorders. Cerebrospinal fluid (CSF) 1 is produced mainly by the choroid plexus within the ventricles of the brain. It circulates through the ventricular system and around the outside of the brain and spinal cord in the subarachnoid space. CSF is clinically accessible through standard lumbar puncture techniques. Because it is in direct contact with the brain interstitial fluid, biochemical changes taking place in the brain are often reflected in CSF. These features make CSF potentially a very useful source of biomarkers for diagnosis and response to treatment as well as for providing information on pathological processes underlying a number of central nervous system disorders, including Alzheimer disease (AD) (for reviews, see Refs. 1 and 2). Based on known pathology and the hypothesized etiology of AD, a few AD biomarkers in CSF have been identified that may differentiate groups of individuals with clinical disease from those who are cognitively normal, including amyloid ␤ (A␤) 42, total tau, phospho-tau, isoprostane, and sulfatide (3-7). Although some candidate biomarkers have shown promise, each has its limitations. Researchers are still searching for biomarkers that have a higher sensitivity and specificity to differentiate AD from normal aging and other dementias, especially in the early stages. It would also be especially useful to develop antecedent biomarkers for AD, considering its estimated preclinical phase of 10 -20 years (8).Ne...

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Section: Fig 3 Representative Gel Images and 3-d Representations Ofsupporting

confidence: 86%

Section: Fig 3 Representative Gel Images and 3-d Representations Ofmentioning

confidence: 93%

Comparative Proteomic Analysis of Intra- and Interindividual Variation in Human Cerebrospinal Fluid

Malone

Fagan

et al. 2005

Molecular & Cellular Proteomics

114

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“…The excitatory amino acid transporter 2 showed oxidation in the AD brain [147]. In the CSF of patients with AD, decreased levels for apolipoproteins, retinol-binding protein, and transthyretin were detected [101,160]. Whereas Puchades et al [101] reported decreased levels for ApoE, Fukuyama et al [161] found increased levels for the protein in the CSF of AD patients.…”

Section: Synaptosomal and Transport Proteinsmentioning

confidence: 99%

Proteomics‐driven progress in neurodegeneration research

Fountoulakis

Κοσσίδα

2006

Electrophoresis

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Proteomics-driven progress in neurodegeneration researchProteomics technologies have been widely used in the investigation of neurodegenerative and psychiatric disorders, and in particular in the detection of differences between healthy individuals and patients suffering from such diseases. Thus, brain and cerebrospinal fluid (CSF) samples from patients with Alzheimer's disease, Down syndrome, Pick's disease, Parkinson's disease, schizophrenia, and other disorders as well as brain and CSF from animals serving as models of neurological disorders have been analyzed by proteomics. 2-DE followed by MALDI-TOF-MS has been mainly applied as this proteomics approach provides the possibility of convenient quantification of protein levels and detection of post-translational modifications. About 330 unique proteins with deranged levels and modifications have been detected by proteomics approaches to be related to neurodegeneration and psychiatric disorders. They are mainly involved in metabolism pathways, cytoskeleton formation, signal transduction, guidance, detoxification, transport, and conformational changes. In this article, we provide a summary of the major contributions of proteomics technologies in the study of neurodegenerative and psychiatric diseases, in particular, in the detection of changes in protein levels and modifications related to these disorders. IntroductionNeurodegeneration is a major hallmark of a series of genetic and acquired disorders of the central nervous system (CNS), like Alzheimer's disease (AD), Down syndrome (DS), Pick's disease, Creutzfeldt-Jakob disease (CJD), and Parkinson's disease, which result in severe cognitive and motor deficits. A common characteristic of these diseases is that they are multifactorial.Their molecular basis is unknown and individual biomarkers are not reliable. Genomics and proteomics approaches have been applied to obtain a better understanding of neurodegeneration and psychiatric disorders. Genomics has been used to map and identify genes that are mutated in a wide variety of such disorders, like presenilins in AD. Next to genomics, which only provides a partial view of the biological problem, proteomics is widely used in clinical diagnosis as well and many changes in protein levels associated with specific diseases have been identified [1,2].Proteomics is a technology-driven science that studies the proteins of the various biological systems, their structures, interactions, post-translational modifications, and in particular the changes in their levels and modifications, which are the result of specific diseases or are induced by external factors.

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“…Indeed, many increasingly more powerful yet complementary proteomics technologies have been leveled at CSF biomarker discovery in the past decade, including: variations of 2D gel electrophoresis [2,20,[22][23][24][25][26][27][28][29][30]; SELDI-TOF-MS [31][32][33][34]; offline LC -MALDI-TOF [35]; and LC-MS/MS with either isotopecoded affinity tags (ICAT) [36], Tandem Mass Tags [37] or iTRAQ (isobaric tag for relative and absolute quantification) [38,39]. These techniques have all been used successfully to identify candidate biomarkers because they provide accurate relative quantitative information between or among samples.…”

Section: Introductionmentioning

confidence: 99%

P1–206: Quantitative label‐free proteomics for discovery of biomarkers in cerebrospinal fluid: Assessment of technical and inter‐individual variation

Perrin

Payton

Malone

et al. 2013

Alzheimer's & Dementia

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Background: Biomarkers are required for pre-symptomatic diagnosis, treatment, and monitoring of neurodegenerative diseases such as Alzheimer's disease. Cerebrospinal fluid (CSF) is a favored source because its proteome reflects the composition of the brain. Ideal biomarkers have low technical and inter-individual variability (subject variance) among control subjects to minimize overlaps between clinical groups. This study evaluates a process of multi-affinity fractionation (MAF) and quantitative label-free liquid chromatography tandem mass spectrometry (LC-MS/MS) for CSF biomarker discovery by (1) identifying reparable sources of technical variability, (2) assessing subject variance and residual technical variability for numerous CSF proteins, and (3) testing its ability to segregate samples on the basis of desired biomarker characteristics.

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Proteome analysis of cerebrospinal fluid proteins in Alzheimer patients

Cited by 186 publications

References 20 publications

Comparative Proteomic Analysis of Intra- and Interindividual Variation in Human Cerebrospinal Fluid

Comparative Proteomic Analysis of Intra- and Interindividual Variation in Human Cerebrospinal Fluid

Proteomics‐driven progress in neurodegeneration research

P1–206: Quantitative label‐free proteomics for discovery of biomarkers in cerebrospinal fluid: Assessment of technical and inter‐individual variation

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