Alzheimer disease pathology and the cerebrospinal fluid proteome

Autor: Jérôme Wojcik, Aikaterini Oikonomidi, John Corthésy, Antonio Núñez Galindo, Gene L. Bowman, India Severin, Ornella Cominetti, Julius Popp, Loïc Dayon, Martin Kussmann, Hugues Henry, Eugenia Migliavacca
Rok vydání: 2018
Předmět:
Proteomics
Male
0301 basic medicine
Pathology
Proteome
Neuropsychological Tests
Tandem mass tag
lcsh:RC346-429
0302 clinical medicine
Cerebrospinal fluid
Tandem Mass Spectrometry
Phosphorylation
Aged
80 and over
Neurodegeneration
Age Factors
Middle Aged
3. Good health
Neurology
Educational Status
Biomarker (medicine)
Female
Alzheimer disease
Alzheimer's disease
Amyloid
medicine.medical_specialty
Cognitive Neuroscience
tau Proteins
CSF
lcsh:RC321-571
03 medical and health sciences
Apolipoproteins E
Sex Factors
medicine
Humans
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
lcsh:Neurology. Diseases of the nervous system
Aged
Amyloid beta-Peptides
Alzheimer Disease/cerebrospinal fluid
Alzheimer Disease/genetics
Alzheimer Disease/pathology
Amyloid beta-Peptides/cerebrospinal fluid
Apolipoproteins E/genetics
Chromatography
Liquid
Peptide Fragments/cerebrospinal fluid
Proteome/metabolism
tau Proteins/cerebrospinal fluid
Biomarker
Mass spectrometry
Tau
business.industry
Research
medicine.disease
Peptide Fragments
Reelin Protein
030104 developmental biology
Neurology (clinical)
business
030217 neurology & neurosurgery
Zdroj: Alzheimer’s Research & Therapy, Vol 10, Iss 1, Pp 1-12 (2018)
Alzheimer's Research & Therapy
Alzheimer's research & therapy, vol. 10, no. 1, pp. 66
ISSN: 1758-9193
DOI: 10.1186/s13195-018-0397-4
Popis: Background Altered proteome profiles have been reported in both postmortem brain tissues and body fluids of subjects with Alzheimer disease (AD), but their broad relationships with AD pathology, amyloid pathology, and tau-related neurodegeneration have not yet been fully explored. Using a robust automated MS-based proteomic biomarker discovery workflow, we measured cerebrospinal fluid (CSF) proteomes to explore their association with well-established markers of core AD pathology. Methods Cross-sectional analysis was performed on CSF collected from 120 older community-dwelling adults with normal (n = 48) or impaired cognition (n = 72). LC-MS quantified hundreds of proteins in the CSF. CSF concentrations of β-amyloid 1–42 (Aβ1–42), tau, and tau phosphorylated at threonine 181 (P-tau181) were determined with immunoassays. First, we explored proteins relevant to biomarker-defined AD. Then, correlation analysis of CSF proteins with CSF markers of amyloid pathology, neuronal injury, and tau hyperphosphorylation (i.e., Aβ1–42, tau, P-tau181) was performed using Pearson’s correlation coefficient and Bonferroni correction for multiple comparisons. Results We quantified 790 proteins in CSF samples with MS. Four CSF proteins showed an association with CSF Aβ1–42 levels (p value ≤ 0.05 with correlation coefficient (R) ≥ 0.38). We identified 50 additional CSF proteins associated with CSF tau and 46 proteins associated with CSF P-tau181 (p value ≤ 0.05 with R ≥ 0.37). The majority of those proteins that showed such associations were brain-enriched proteins. Gene Ontology annotation revealed an enrichment for synaptic proteins and proteins originating from reelin-producing cells and the myelin sheath. Conclusions We used an MS-based proteomic workflow to profile the CSF proteome in relation to cerebral AD pathology. We report strong evidence of previously reported CSF proteins and several novel CSF proteins specifically associated with amyloid pathology or neuronal injury and tau hyperphosphorylation. Electronic supplementary material The online version of this article (10.1186/s13195-018-0397-4) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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