title: Cholesterol, oxysterol, triglyceride, and coenzyme Q homeostasis in ALS. Evidence against the hypothesis that elevated 27-hydroxycholesterol is a pathogenic factor.
abstract: High plasma levels of cholesterol have been suggested to be neuroprotective for the degenerative disease amyotrophic lateral sclerosis (ALS) and to be associated with increased survival time. The gene encoding cholesterol 27-hydroxylase, CYP27A1, was recently identified as a susceptibility gene for sporadic ALS. A product of this enzyme is 27-hydroxycholesterol. We investigated plasma samples from 52 ALS patients and 40 control subjects (spouses) regarding cholesterol homeostasis, lipid profiles, and coenzyme Q. Eleven of the patients carried mutations in C9orf72 and seven in SOD1. Plasma levels of 27-hydroxycholesterol were significantly lower in male patients with ALS than in controls. It was not possible to link the reduced levels to any specific mutation, and there was no significant correlation between 27-hydroxycholesterol and survival. With normalization for diet using the spouses, a correlation was found between survival and total cholesterol, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, and coenzyme Q. We conclude that cholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 27-hydroxycholesterol and lipid profiles in plasma are of limited prognostic value in individual ALS patients.
authors.affiliation: Computational Lifescience Cluster (CLiC), Umeå University, Umeå, Sweden; Department of Chemistry, Umeå University, Umeå, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Wuolikainen
authors.affiliation: Department of Laboratory Medicine, Karolinska Institute, Huddinge, Sweden.
authors.forename: Jure
authors.initials: J
authors.lastname: Acimovic
authors.affiliation: Department of Laboratory Medicine, Karolinska Institute, Huddinge, Sweden.
authors.forename: Anita
authors.initials: A
authors.lastname: Lövgren-Sandblom
authors.affiliation: Department of Laboratory Medicine, Karolinska Institute, Huddinge, Sweden.
authors.forename: Paolo
authors.initials: P
authors.lastname: Parini
authors.affiliation: Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Andersen
authors.affiliation: Department of Laboratory Medicine, Karolinska Institute, Huddinge, Sweden.
authors.forename: Ingemar
authors.initials: I
authors.lastname: Björkhem
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000235:genetics / Q000401:mortality; D000073885:C9orf72 Protein; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006706:Homeostasis; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009154:Mutation; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D015996:Survival Rate; D014280:Triglycerides / Q000097:blood*; D014451:Ubiquinone / Q000097:blood*
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D006888:Hydroxycholesterols; D011506:Proteins; C000606290:SOD1 protein, human; D014280:Triglycerides; D014451:Ubiquinone; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1