title: Human cerebrospinal fluid fatty acid levels differ between supernatant fluid and brain-derived nanoparticle fractions, and are altered in Alzheimer's disease.
abstract: BACKGROUND
  Although saturated (SAFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids are important structural components of neuronal membranes and precursors of signaling molecules, knowledge of their metabolism in Alzheimer's disease (AD) is limited. Based on recent discovery that lipids in cerebrospinal fluid (CSF) are distributed in both brain-derived nanoparticles (NP) and supernatant fluid (SF), we hypothesized that fatty acid (FA) abundance and distribution into these compartments is altered in early AD pathology.
  
  
  RESULTS
  We assayed the FA composition and abundance in CSF fractions from cognitively healthy (CH), mild cognitive impairment (MCI), and AD study participants using gas chromatography-mass spectrometry. In the SF fraction, concentration of docosahexaenoic acid [DHA, (C22:6n-3)] was less in AD compared with CH, while alpha linolenic acid [α-LNA, (C18:3n-3)] was lower in MCI compared with CH. In the NP fraction, levels of SAFAs (C15:0, C16:0) and a MUFA (C15:1) differentiated CH from MCI, while two MUFAs (C15:1, C19:1) and four PUFAs (C20:2n-6, C20:3n-3, C22:4n-6, C22:5n-3) were higher in AD compared with CH. Levels of even-chain free SAFA and total free FA levels were higher in AD, levels of odd-chain free SAFAs, MUFAs, n-3 PUFAs, and total PUFA, were lower in AD compared with CH. Free n-6 PUFA levels were similar in all three groups.
  
  
  CONCLUSIONS
  FA metabolism is compartmentalized differently in NP versus SF fractions of CSF, and altered FA levels reflect the importance of abnormal metabolism and oxidative pathways in AD. Depleted DHA in CSF fractions in AD is consistent with the importance of n-3 PUFAs in cognitive function, and suggests that disturbed PUFA metabolism contributes to AD pathology. This study of FA levels in CSF fractions from different cognitive stages shows potential AD biomarkers, and provides further insight into cell membrane dysfunctions, including mechanisms leading to amyloid production.
authors: Molecular Neurology Program, Huntington Medical Research Institutes, Pasadena, California, United States of America.
authors: Alfred N
authors: AN
authors: Fonteh
authors: Molecular Neurology Program, Huntington Medical Research Institutes, Pasadena, California, United States of America.
authors: Matthew
authors: M
authors: Cipolla
authors: Molecular Neurology Program, Huntington Medical Research Institutes, Pasadena, California, United States of America.
authors: Jiarong
authors: J
authors: Chiang
authors: Molecular Neurology Program, Huntington Medical Research Institutes, Pasadena, California, United States of America.
authors: Xianghong
authors: X
authors: Arakaki
authors: Molecular Neurology Program, Huntington Medical Research Institutes, Pasadena, California, United States of America.
authors: Michael G
authors: MG
authors: Harrington
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism*; D001826:Body Fluids / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000378:metabolism; D005227:Fatty Acids / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D008297:Male; D053758:Nanoparticles; D011379:Prognosis
chemical_list: D005227:Fatty Acids