Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019;72(1):127-137.
doi: 10.3233/JAD-190132.

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

Affiliations
Free PMC article

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

Olli Jääskeläinen et al. J Alzheimers Dis. .
Free PMC article

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.

Keywords: C9orf72 protein; cholesterol; frontotemporal lobar degeneration; frontotemporal dementia; inflammation; lipoproteins.

Conflict of interest statement

Authors’ disclosures available online (https://www.j-alz.com/manuscript-disclosures/19-0132r2).

Figures

Fig.1
Fig.1
Differences in the concentrations of serum total cholesterol in HDL (A), LDL (B), and VLDL (C) between C9orf72 repeat expansion carriers and non-carriers. Total serum cholesterol concentrations in HDL are significantly lower in the repeat expansion carriers when compared to non-carriers. *statistically significant difference, p = 0.030; C9orf72, Chromosome 9 open reading frame 72; HDL, high-density lipoprotein; LDL, low-density lipoprotein; VLDL, very low-density lipoprotein.

Similar articles

See all similar articles

Cited by 1 article

References

    1. Ratnavalli E, Brayne C, Dawson K, Hodges JR (2002) The prevalence of frontotemporal dementia. Neurology 58, 1615–1621. - PubMed
    1. Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, van Swieten JC, Seelaar H, Dopper EGP, Onyike CU, Hillis AE, Josephs KA, Boeve BF, Kertesz A, Seeley WW, Rankin KP, Johnson JK, Gorno-Tempini M-L, Rosen H, Prioleau-Latham CE, Lee A, Kipps CM, Lillo P, Piguet O, Rohrer JD, Rossor MN, Warren JD, Fox NC, Galasko D, Salmon DP, Black SE, Mesulam M, Weintraub S, Dickerson BC, Diehl-Schmid J, Pasquier F, Deramecourt V, Lebert F, Pijnenburg Y, Chow TW, Manes F, Grafman J, Cappa SF, Freedman M, Grossman M, Miller BL (2011) Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 134, 2456–2477. - PMC - PubMed
    1. Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, Ogar JM, Rohrer JD, Black S, Boeve BF, Manes F, Dronkers NF, Vandenberghe R, Rascovsky K, Patterson K, Miller BL, Knopman DS, Hodges JR, Mesulam MM, Grossman M (2011) Classification of primary progressive aphasia and its variants. Neurology 76, 1006–1014. - PMC - PubMed
    1. Rohrer JD, Guerreiro R, Vandrovcova J, Uphill J, Reiman D, Beck J, Isaacs AM, Authier A, Ferrari R, Fox NC, Mackenzie IRA, Warren JD, de Silva R, Holton J, Revesz T, Hardy J, Mead S, Rossor MN (2009) The heritability and genetics of frontotemporal lobar degeneration. Neurology 73, 1451–1456. - PMC - PubMed
    1. Benussi A, Padovani A, Borroni B (2015) Phenotypic heterogeneity of monogenic frontotemporal dementia. Front Aging Neurosci 7, 171. - PMC - PubMed

LinkOut - more resources

Feedback