Cerebrospinal fluid fatty acid composition changes in Alzheimer’s disease (651.7)

Abstract

Objectives: To test the hypothesis that levels of saturated fatty acids (SAFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) that are structural components of neuronal membranes or are precursors of signaling molecules change in Alzheimer’s disease (AD).Methods: We recruited and collected cerebrospinal fluid (CSF) from cognitively healthy (CH), mild cognitively impairment (MCI), and AD study participants. After fractionation of CSF into a 200,000 g supernatant fluid (SF) and nanoparticle (NP) fractions, we used gas chromatography‐ negative ion chemical ionization/mass spectrometry to determine the total fatty acid composition of these fractions.Results: Levels of some SAFA, MUFA, and PUFA differed between the SF and NP fractions. Docosahexaenoic acid [DHA, (C22:6, n‐6)] levels were lower in AD compared with CH while alpha linoleic acid [α‐LNA, (C18:3, n‐3)] levels were lower in MCI compared with CH in the SF fraction. In the NP fraction, levels of SAFAs (C15:0, C16:0) and a MUFA (C15:1) differentiated CH from MCI while levels of MUFAs (C15:1, C19:1) and PUFAs (C20:2, C20:3, C22:4, C22:5) were altered in AD compared with CH.Conclusions: Fatty acid metabolism is compartmentalized in CSF fractions and differences between clinical groups suggest that energy metabolism or oxidative pathways are important in AD pathophysiology. Some fatty acids in CSF fractions may be biomarkers of AD. Thus, dietary or pharmacological approaches to regulate brain fatty acid levels and measurement of fatty acid in CSF fractions may be helpful in prevention or monitoring AD.Grant Funding Source: L.K. Whittier and the Helen Posthuma Foundations