Plasma and brain fatty acid profiles in mild cognitive impairment and Alzheimer's disease

Abstract

Alzheimer's disease (AD) is generally associated with lower omega-3 fatty acid intake from fish but despite numerous studies, it is still unclear whether there are differences in omega-3 fatty acids in plasma or brain. In matched plasma and brain samples provided by the Memory and Aging Project, fatty acid profiles were quantified in several plasma lipid classes and in three brain cortical regions. Fatty acid data were expressed as % composition and as concentrations (mg/dL for plasma or mg/g for brain). Differences in plasma fatty acid profiles between AD, mild cognitive impairment (MCI), and those with no cognitive impairment (NCI) were most apparent in the plasma free fatty acids (lower oleic acid isomers and omega-6 fatty acids in AD) and phospholipids (lower omega-3 fatty acids in AD). In brain, % DHA was lower only in phosphatidylserine of mid-frontal cortex and superior temporal cortex in AD compared to NCI (-14% and -12%, respectively; both p < 0.05). The only significant correlation between plasma and brain fatty acids was between % DHA in plasma total lipids and % DHA in phosphatidylethanolamine of the angular gyrus, but only in the NCI group (+0.77, p < 0.05). We conclude that AD is associated with altered plasma status of both DHA and other fatty acids unrelated to DHA, and that the lipid class-dependent nature of these differences reflects a combination of differences in intake and metabolism.

Fig. 1

Docosahexaenoic acid (DHA) in plasma total lipids (TL), triglycerides (TG), cholesteryl esters (CE), free fatty acids (FFA) and phospholipids (PL) expressed as % composition (upper panel) or concentration (mg/dL; lower panel). Bars are for no cognitive impairment (■, n = 10), mild cognitive impairment (□, n = 7), or Alzheimer’s disease ( , n = 9). Data for Alzheimer’s disease were significantly different from the no cognitive impairment group and/or the mild cognitive impairment group (*p < 0.05; Kruskal-Wallis followed by Mann-Whitney tests).

Fig. 2

Percent composition of docosahexaenoic acid in brain phos-phatidylserine (% DHA-PS) in three brain regions in persons with no cognitive impairment. Bars are for no cognitive impairment (■, n = 12), mild cognitive impairment ( , n = 12), or Alzheimer’s disease (□, n = 12). Data for Alzheimer’s disease were significantly different from both no cognitive impairment and mild cognitive impairment groups in the midfrontal cortex (**p = 0.014; Kruskal-Wallis followed by Mann Whitney tests) and in the superior temporal cortex (*p = 0.03; Kruskal-Wallis test). No other differences in fatty acid composition for these brain regions were observed across the three groups, or across the four brain phospholipid classes studied, regardless of whether the data were expressed as concentration (mg/g) or % composition.

Fig. 3

Significant positive correlation between percent composition of docosahexaenoic acid in plasma total lipids [DHA-Plasma TL (%)] versus % DHA in phosphatidylethanolamine of the brain’s angular gyrus [DHA-PE (%)] in the no cognitive impairment group (n = 11; r = +0.77, p = 0.005). In the Alzheimer’s disease and mild cognitive impairment groups, there was no significant correlation between docosahexaenoic acid in any plasma lipid class compared to any brain lipid class or brain region.