University of Oulu

Olli Jääskeläinen, Eino Solje, Anette Hall, Kasper Katisko, Ville Korhonen, Mika Tiainen, … Sanna-Kaisa Herukka. (2019). Low Serum High-Density Lipoprotein Cholesterol Levels Associate with the C9orf72 Repeat Expansion in Frontotemporal Lobar Degeneration Patients. Journal of Alzheimer’s Disease, 72(1), 127–137. https://doi.org/10.3233/JAD-190132

Low serum high-density lipoprotein cholesterol levels associate with the C9orf72 repeat expansion in frontotemporal lobar degeneration patients

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Author: Jääskeläinen, Olli1; Solje, Eino1,2; Hall, Anette1;
Organizations: 1Institute of Clinical Medicine–Neurology, University of Eastern Finland, Kuopio, Finland
2Neuro Center, Kuopio University Hospital, Kuopio, Finland
3Institute of Clinical Medicine – Neurosurgery, University of Eastern Finland, Kuopio, Finland
4NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
5Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland
6Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
7Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK
8Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK
9Systems Epidemiology, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
10Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, VIC, Australia
11A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
12Medical Research Center, Oulu University Hospital, Oulu, Finland
13Research Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.1 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe202003067592
Language: English
Published: IOS Press, 2019
Publish Date: 2020-03-06
Description:

Abstract

Decreased levels of serum high-density lipoprotein (HDL) cholesterol have previously been linked to systemic inflammation and neurodegenerative diseases, such as Alzheimer’s disease. Here, we aimed to analyze the lipoprotein profile and inflammatory indicators, the high-sensitivity C-reactive peptide (hs-CRP) and glycoprotein acetyls (GlycA), in sporadic and C9orf72 repeat expansion-associated frontotemporal lobar degeneration (FTLD) patients. The C9orf72 hexanucleotide repeat expansion is the most frequent genetic etiology underlying FTLD. The concentrations of different lipid measures in the sera of 67 FTLD patients (15 C9orf72 repeat expansion carriers), including GlycA, were analyzed by nuclear magnetic resonance spectroscopy. To verify the state of systemic inflammation, hs-CRP was also quantified from patient sera. We found that the total serum HDL concentration was decreased in C9orf72 repeat expansion carriers when compared to non-carriers. Moreover, decreased concentrations of HDL particles of different sizes and subclass were consistently observed. No differences were detected in the very low- and low-density lipoprotein subclasses between the C9orf72 repeat expansion carriers and non-carriers. Furthermore, hs-CRP and GlycA levels did not differ between the C9orf72 repeat expansion carriers and non-carriers. In conclusion, the HDL-related changes were linked with C9orf72 repeat expansion associated FTLD but were not seen to associate with systemic inflammation. The underlying reason for the HDL changes remains unclear.

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Series: Journal of Alzheimer's disease
ISSN: 1387-2877
ISSN-E: 1875-8908
ISSN-L: 1387-2877
Volume: 72
Issue: 1
Pages: 127 - 137
DOI: 10.3233/JAD-190132
OADOI: https://oadoi.org/10.3233/JAD-190132
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
Subjects:
Funding: Technical laboratory assistance was provided by Tarja Kauppinen, Päivi Räsänen, and Anne Kaikko. Proofreading of the manuscript was conducted by Elsa Language Services (Kuopio, Finland). Olli Jääskeläinen has received a personal grant from Emil Aaltonen Foundation. Olli Jääskeläinen, Sanna-Kaisa Herukka, Annakaisa Haapasalo, Mikko Hiltunen, and Hilkka Soininen are part of the EU H2020-TWINN SynaNet, ‘Neurologic and Psychiatric Disorders: from synapses to network’ consortium, funded by the European Horizon 2020 research and innovation program (grant number 692340). Annakaisa Haapasalo and Anne M. Remes are supported by the Academy of Finland (grant numbers 315459 and 2315460). Mika Ala-Korpela is supported by a Senior Research Fellowship from the National Health and Medical Research Council (NHMRC) of Australia (APP1158958). He also works in a unit that is supported by the University of Bristol and UK Medical Research Council (MC UU 12013/1). The Baker Institute is supported in part by the Victorian Government’s Operational Infrastructure Support Program.
Academy of Finland Grant Number: 315459
2315460
Detailed Information: 315459 (Academy of Finland Funding decision)
2315460 (Academy of Finland Funding decision)
Copyright information: © 2019 – IOS Press and the authors. All rights reserved. This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0).
  https://creativecommons.org/licenses/by/4.0/