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Novel cerebrospinal fluid biomarkers of axonal degeneration in frontotemporal dementia.

Artikel i vetenskaplig tidskrift
Författare Niklas Mattsson
Ulla Rüetschi
Yolande A L Pijnenburg
Marinus A Blankenstein
Vladimir N Podust
Susann Li
Inger Fagerberg
Lars Rosengren
Kaj Blennow
Henrik Zetterberg
Publicerad i Molecular medicine reports
Volym 1
Nummer/häfte 5
Sidor 757-61
ISSN 1791-2997
Publiceringsår 2008
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 757-61
Språk en
Länkar dx.doi.org/10.3892/mmr_00000025
Ämneskategorier Psykiatri

Sammanfattning

Frontotemporal dementia (FTD) is a heterogeneous disease with substantial interpersonal variance in aggressiveness. Novel biomarkers for rapidly progressive FTD could improve diagnosis and provide clues regarding its pathogenesis. In this study, surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS) was used to analyze peptide profiles in cerebrospinal fluid (CSF) from 24 FTD patients. Thirteen patients had rapidly progressive FTD with distinct pathology in a brain MRI after less than 3 years of disease duration. Eleven patients had slowly progressive FTD with a normal brain MRI, but had abnormal findings in SPECT/PET after more than 5 years of disease duration. The axonal damage marker CSF neurofilament light-chain (NF-L) was measured in all subjects to evaluate the amount of axonal degeneration. A CSF NF-L level of 150 ng/l was used as a cut-off point for high NF-L expression. SELDI-TOF analysis of peptides in the range of 2000-20000 m/z revealed one peak with m/z of 6378 that was expressed at a significantly different level (p<0.01) when rapidly versus slowly progressive cases of FTD were compared. Eleven peaks were expressed at different levels when high versus low CSF NF-L were compared. Using chromatographic purification followed by tandem mass spectrometric analysis, five of these peaks were identified as follows: C-terminal fragment of neuroendocrine protein 7B2 (3512.84 Da), C-terminal fragment of osteopontin (7658.19 Da) as well as its mono- and diphosphorylated forms (7738.16 Da and 7818.13 Da, respectively) and pancreatic ribonuclease (14566.33 Da). The peak intensity of pancreatic ribonuclease was higher in patients with low NF-L expression, while the other peptides had a lower peak intensity in this group. Altered levels of these peptides have also been described in other neurodegenerative diseases. Taken together, these data suggest that differentially-expressed peptides are general markers of axonal degeneration. Further studies are needed to verify their prognostic value in FTD.

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