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Indices of fatty acyl‐CoA desaturase activity are associated with cognitive function and preclinical changes in cerebrospinal fluid beta‐amyloid and tau levels in Alzheimer's disease
Author(s) -
Fonteh Alfred N.,
Cipolla Matthew,
Chiang Jiarong,
Arakaki Xianghong,
Harrington Michael
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.625.3
Subject(s) - cerebrospinal fluid , chemistry , medicine , fatty acid , endocrinology , biochemistry
Objectives To determine if indices of acyl‐CoA desaturase can differentiate stages of dementia. Methods We used gas chromatography‐mass spectrometry to quantify saturated (SAFA) and monounsaturated (MUFA) fatty acids in cerebrospinal fluid (CSF) fractions from cognitively normal study participants (CN, n=70), study participants with mild cognitive impairment (MCI, n=40), and Alzheimer's disease (AD, n=29). CSF amyloid and tau measures revealed two CN groups: CN with normal Aβ42/tau (CN‐nAT, n=36) and CN with pathological Aβ42/tau (CN‐pAT, n=34). We determined the ratio of each MUFA product to their corresponding SAFA precursor for even numbered (C14:1/C14:0, C16:1/C16:0, C18:1/C18:0) and odd numbered (C15:1/C15:0, C17:1/C17:0, C19:1/C19:0) chain fatty acids. Results The product to substrate ratio (desaturase index) was different in the CSF nanoparticle fraction (NP) compared with the supernatant fluid (SF) or free fatty acid fractions. C18:1/C18:0 accounted for most of the desaturation index in CSF fractions. In the NP fraction, desaturation index progressively decreased in MCI and AD compared with CN. ROC curves show that free C18:1/C18:0 indices can differentiate CN from MCI and MCI from AD. Conclusions The rate‐limiting enzyme in the biosynthesis of MUFAs, stearoyl‐CoA desaturase (SCD‐1), is altered with cognitive changes. Desaturation indices for free fatty acids in CSF can differentiate CN from MCI and AD and are altered in pre‐symptomatic AD. These changes may reflect changes in energy balance, pro‐inflammatory parameters, or membrane properties linked to amyloid precursor protein processing. Support or Funding Information L.K. Whittier and the Helen Posthuma Foundations