Low Serum High-Density Lipoprotein Cholesterol Levels Associate with the C9orf72 Repeat Expansion in Frontotemporal Lobar Degeneration Patients

Olli Jääskeläinen, Eino Solje, Anette Hall, Kasper Katisko, Ville Korhonen, Mika Tiainen, Antti J Kangas, Seppo Helisalmi, Maria Pikkarainen, Anne Koivisto, Päivi Hartikainen, Mikko Hiltunen, Mika Ala-Korpela, Hilkka Soininen, Pasi Soininen, Annakaisa Haapasalo, Anne M Remes, Sanna-Kaisa Herukka

Research output: Contribution to journalArticle (Academic Journal)

5 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)127 - 137
Number of pages11
JournalJournal of Alzheimer's Disease
Volume72
Early online date29 Oct 2019
DOIs
Publication statusE-pub ahead of print - 29 Oct 2019

Keywords

  • C9orf72 protein
  • cholesterol
  • frontotemporal dementia
  • frontotemporal lobar degeneration
  • inflammation
  • lipoproteins

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