Elevated stearoyl-CoA desaturase in brains of patients with Alzheimer's disease

PLoS One. 2011;6(10):e24777. doi: 10.1371/journal.pone.0024777. Epub 2011 Oct 26.

Abstract

The molecular bases of Alzheimer's disease (AD) remain unclear. We used a lipidomic approach to identify lipid abnormalities in the brains of subjects with AD (N = 37) compared to age-matched controls (N = 17). The analyses revealed statistically detectable elevations in levels of non-esterified monounsaturated fatty acids (MUFAs) and mead acid (20:3n-9) in mid-frontal cortex, temporal cortex and hippocampus of AD patients. Further studies showed that brain mRNAs encoding for isoforms of the rate-limiting enzyme in MUFAs biosynthesis, stearoyl-CoA desaturase (SCD-1, SCD-5a and SCD-5b), were elevated in subjects with AD. The monounsaturated/saturated fatty acid ratio ('desaturation index')--displayed a strong negative correlation with measures of cognition: the Mini Mental State Examination test (r = -0.80; P = 0.0001) and the Boston Naming test (r = -0.57; P = 0.0071). Our results reveal a previously unrecognized role for the lipogenic enzyme SCD in AD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8,11,14-Eicosatrienoic Acid / analogs & derivatives*
  • 8,11,14-Eicosatrienoic Acid / analysis
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / enzymology*
  • Alzheimer Disease / etiology
  • Brain / metabolism*
  • Brain Mapping
  • Case-Control Studies
  • Cognition
  • Fatty Acids, Monounsaturated / analysis*
  • Female
  • Humans
  • Male
  • Metabolic Networks and Pathways
  • Protein Isoforms / analysis
  • RNA, Messenger / analysis
  • Stearoyl-CoA Desaturase / genetics
  • Stearoyl-CoA Desaturase / metabolism*

Substances

  • Fatty Acids, Monounsaturated
  • Protein Isoforms
  • RNA, Messenger
  • Stearoyl-CoA Desaturase
  • 8,11,14-Eicosatrienoic Acid
  • mead acid

Associated data

  • RefSeq/NM_001037582
  • RefSeq/NM_024906