Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital

Distinct transthyretin oxidation isoform profile in spinal fluid from patients with Alzheimer's disease and mild cognitive impairment

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


  1. Discovery and validation of a colorectal cancer classifier in a new blood test with improved performance for high-risk subjects

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Distinct proteome pathology of circulating microparticles in systemic lupus erythematosus

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Serum proteome pool changes in type 2 diabetic patients treated with anakinra

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Ageing as a risk factor for neurodegenerative disease

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  2. Automatically computed rating scales from MRI for patients with cognitive disorders

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Exercise as a potential modulator of inflammation in patients with Alzheimer's disease measured in cerebrospinal fluid and plasma

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Ventriculoperitoneal Shunt Complications in the European Idiopathic Normal Pressure Hydrocephalus Multicenter Study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

BACKGROUND: Transthyretin (TTR), an abundant protein in cerebrospinal fluid (CSF), contains a free, oxidation-prone cysteine residue that gives rise to TTR isoforms. These isoforms may reflect conditions in vivo. Since increased oxidative stress has been linked to neurodegenerative disorders such as Alzheimer's disease (AD) it is of interest to characterize CSF-TTR isoform distribution in AD patients and controls. Here, TTR isoforms are profiled directly from CSF by an optimized immunoaffinity-mass spectrometry method in 76 samples from patients with AD (n = 37), mild cognitive impairment (MCI, n = 17)), and normal pressure hydrocephalus (NPH, n = 15), as well as healthy controls (HC, n = 7). Fractions of three specific oxidative modifications (S-cysteinylation, S-cysteinylglycinylation, and S-glutathionylation) were quantitated relative to the total TTR protein. Results were correlated with diagnostic information and with levels of CSF AD biomarkers tau, phosphorylated tau, and amyloid β1-42 peptide.

RESULTS: Preliminary data highlighted the high risk of artifactual TTR modification due to ex vivo oxidation and thus the samples for this study were all collected using strict and uniform guidelines. The results show that TTR is significantly more modified on Cys(10) in the AD and MCI groups than in controls (NPH and HC) (p ≤ 0.0012). Furthermore, the NPH group, while having normal TTR isoform distribution, had significantly decreased amyloid β peptide but normal tau values. No obvious correlations between levels of routine CSF biomarkers for AD and the degree of TTR modification were found.

CONCLUSIONS: AD and MCI patients display a significantly higher fraction of oxidatively modified TTR in CSF than the control groups of NPH patients and HC. Quantitation of CSF-TTR isoforms thus may provide diagnostic information in patients with dementia symptoms but this should be explored in larger studies including prospective studies of MCI patients. The development of methods for simple, robust, and reproducible inhibition of in vitro oxidation during CSF sampling and sample handling is highly warranted. In addition to the diagnostic information the possibility of using TTR as a CSF oxymeter is of potential value in studies monitoring disease activity and developing new drugs for neurodegenerative diseases.

TidsskriftClinical Proteomics
Udgave nummer1
Sider (fra-til)12
Antal sider9
StatusUdgivet - 29 mar. 2014

ID: 44458981