Jeppsson, A;
Höltta, M;
Zetterberg, H;
Blennow, K;
Wikkelsø, C;
Tullberg, M;
(2016)
Amyloid mis-metabolism in idiopathic normal pressure hydrocephalus.
Fluids and Barriers of the CNS
, 13
, Article 13. 10.1186/s12987-016-0037-y.
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Abstract
BACKGROUND: Patients with idiopathic normal pressure hydrocephalus (iNPH) have reduced cerebrospinal fluid (CSF) concentrations of amyloid-β (Aβ) and α- and β-cleaved soluble forms of amyloid precursor protein (sAPPα and sAPPβ). The aims of this study were to examine if changes could also be seen in the CSF for secreted metabolites of APP-like protein 1 (APLP1) and to explore the prognostic value of amyloid-related CSF biomarkers, as well as markers of neuronal injury and astroglial activation, as regards to clinical outcome after shunt surgery. METHODS: Twenty patients diagnosed with iNPH, 10 improved and 10 unchanged by shunt surgery, and 20 neurologically healthy controls were included. All patients were examined clinically prior to surgery and at 6-month follow-up after surgery using the iNPH scale. Lumbar puncture was performed pre-operatively. CSF samples were analyzed for neurofilament light (NFL), Aβ isoforms Aβ38, Aβ40 and Aβ42, sAPPα, sAPPβ, APLP1 β-derived peptides APL1β25, APL1β 27 and APL1β 28 and YKL40 by immunochemical methods. RESULTS: The concentrations of all soluble forms of APP, all Aβ isoforms and APL1β28 were lower, whilst APL1β25 and APL1β27 were higher in the CSF of iNPH patients compared to controls. There was no difference in biomarker concentrations between patients who improved after surgery and those who remained unchanged. CONCLUSIONS: The reduced CSF concentrations of Aβ38, Aβ40, Aβ42, sAPPα and sAPPβ suggest that APP expression could be downregulated in iNPH. In contrast, APLP1 concentration in the CSF seems relatively unchanged. The increase of APL1β25 and APL1β27 in combination with a slight decreased APL1β28 could be caused by more available γ-secretase due to reduced availability of its primary substrate, APP. The data did not support the use of these markers as indicators of shunt responsiveness.
| Type: | Article |
|---|---|
| Title: | Amyloid mis-metabolism in idiopathic normal pressure hydrocephalus |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s12987-016-0037-y |
| Publisher version: | http://doi.org/10.1186/s12987-016-0037-y |
| Language: | English |
| Additional information: | © 2016 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
| Keywords: | APLP1, Amyloid, Cerebrospinal fluid, NFL, Neurodegeneration, Normal pressure hydrocephalus, Prediction, YKL40 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1537439 |
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