Defective cholesterol metabolism in amyotrophic lateral sclerosis

Jonas Abdel-Khalik, Eylan Yutuc, Peter J Crick, Jan-Åke Gustafsson, Margaret Warner, Gustavo Roman, Kevin Talbot, Elizabeth Gray, William J Griffiths, Martin R Turner, Yuqin Wang

Research output: Contribution to journalArticlepeer-review

94 Scopus citations


As neurons die cholesterol is released in the central nervous system (CNS), hence this sterol and its metabolites may represent a biomarker of neurodegeneration, including in amyotrophic lateral sclerosis (ALS) in which altered cholesterol levels have been linked to prognosis. More than 40 different sterols were quantified in serum and cerebrospinal fluid (CSF) from ALS patients and healthy controls. In CSF the concentration of cholesterol was found to be elevated in ALS samples. When CSF metabolite levels were normalised to cholesterol, the cholesterol metabolite 3beta,7alpha-dihydroxycholest-5-en-26-oic acid, along with its precursor 3beta-hydroxycholest-5-en-26-oic acid and product 7alpha-hydroxy-3-oxocholest-4-en-26-oic acid were reduced in concentration, whereas metabolites known to be imported from the circulation into the CNS were not found to differ in concentration between groups. Analysis of serum revealed that (25R)26-hydroxycholesterol, the immediate precursor of 3beta-hydroxycholest-5-en-26-oic acid was reduced in concentration in ALS patients compared to controls. We conclude that the acidic branch of bile acid biosynthesis, known to operative in-part in brain, is defective in ALS leading to a failure of the CNS to remove excess cholesterol which may be toxic to neuronal cells, compounded by a reduction in neuroprotective 3beta,7alpha-dihydroxycholest-5-en-26-oic acid.

Original languageEnglish (US)
Pages (from-to)267-278
Number of pages12
JournalJournal of lipid research
Issue number1
StatePublished - Nov 3 2016


  • Bile acids and salts/biosynthesis
  • Brain lipids
  • Cholestenoic acids
  • Cytochrome p450
  • Mass spectrometry
  • Neurodeneneration
  • Nuclear receptors/lxr
  • Oxysterols

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology


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