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.

Carrying the apoE e4 allele (E4þ ) is the most important genetic risk for Alzheimer's disease. Unlike non-carriers (E42 ), E4þ seem not to be protected against Alzheimer's disease when consuming fish. We hypothesised that this may be linked to a disturbance in n-3 DHA metabolism in E4þ. The aim of the present study was to evaluate [ 13 C]DHA metabolism over 28 d in E4þ v. E42. A total of forty participants (twenty-six women and fourteen men) received a single oral dose of 40 mg [ 13 C]DHA, and its metabolism was monitored in blood and breath over 28 d. Of the participants, six were E4þ and thirty-four were E42. In E4þ, mean plasma [ 13 C]DHA was 31 % lower than that in E42, and cumulative b-oxidation of [ 13 C]DHA was higher than that in E42 1-28 d post-dose (P#0·05). A genotype £ time interaction was detected for cumulative b-oxidation of [ 13 C]DHA (P#0·01). The whole-body half-life of [ 13 C]DHA was 77 % lower in E4þ compared with E42 (P#0·01). In E4þ and E42, the percentage dose of [ 13 C]DHA recovered/h as 13 CO 2 correlated with [ 13 C]DHA concentration in plasma, but the slope of linear regression was 117 % steeper in E4þ compared with E42 (P# 0·05). These results indicate that DHA metabolism is disturbed in E4þ, and may help explain why there is no association between DHA levels in plasma and cognition in E4þ. However, whether E4þ disturbs the metabolism of 13 C-labelled fatty acids other than DHA cannot be deduced from the present study.

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Objective:To assess odor identification (OI) as an indicator of presymptomatic Alzheimer disease (AD) pathogenesis in cognitively normal aging individuals at increased risk of AD dementia.Methods:In 274 members of the PREVENT-AD cohort of healthy aging persons with a parental or multiple-sibling history of AD dementia, we assessed the cross-sectional association of OI with potential indicators of presymptomatic AD. Some 101 participants donated CSF, thus enabling assessment of AD pathology with the biomarkers total tau (t-tau), phospho-tau (P181-tau), and their ratios with β-amyloid (Aβ1-42). Adjusted analyses considered age, cognition, APOE ε4 status, education, and sex as covariates. We measured OI using the University of Pennsylvania Smell Identification Test and cognitive performance using the Repeatable Battery for Assessment of Neuropsychological Status. Standard kits provided assays of the AD biomarkers. Analyses used robust-fit linear regression models.Results:Reduced OI was associated with lower cognitive score and older age, as well as increased ratios of CSF t-tau and P181-tau to Aβ1-42 (all p < 0.02). However, the observed associations of OI with age and cognition were unapparent in adjusted models that restricted observations to CSF donors and included AD biomarkers. OI showed little association with CSF Aβ1-42 alone except in APOE ε4 carriers having lowest-quartile Aβ1-42 levels.Conclusions:These findings from healthy high-risk older individuals suggest that OI reflects degree of preclinical AD pathology, while its relationships with age and cognition result from the association of these latter variables with such pathology. Diminished OI may be a practical and affordable biomarker of AD pathology.

Elderly people in relatively good health have a similar capacity to produce ketones and to oxidize 13C-beta-hydroxybutyrate as middle-aged or young adults, but oxidize 13C-glucose a little more rapidly than healthy middle-aged adults.

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