Figure 1.
Scheme illustrating fatty acid biosynthesis, metabolism, and function.
A) We detected several even-chain saturated fatty acids (SAFAs) in CSF fractions that may be formed by elongase activity that adds two successive carbons during fatty acid synthesis. These SAFAs may be converted by delta 9 desaturase to mono-unsaturated fatty acids (MUFAs). The NP fractions of CSF are also enriched with odd-chain SAFAs and odd-chain MUFAs likely derived from plants or microbiota. SAFA and MUFA levels are differentially altered in cognitive groups indicating disease progression when CH>MCI>AD, or a different pathological mechanism when the profiles are different. B) Polyunsaturated fatty acids (PUFA) are derived from the successive elongation and desaturation of two essential fatty acids: linoleic acid (LA, 18:2n-6) is the precursor of the n-6 PUFA family while alpha linolenic acid (LNA, 18:3n-3) is the precursor of the n-3 PUFA family. Enzymes or non-enzymatic oxidation of these PUFAs form inflammatory eicosanoids and isoprostanes, respectively. The major n-3 PUFAs (EPA, DHA) are metabolized to anti-inflammatory molecules. PUFA levels are differentially altered in cognitive groups suggesting disease progression when CH>MCI>AD, or a different pathological mechanism when the profiles are different.
Table 1.
Demographic data, APOE genotype, and CSF levels of Aβ1-42 and tau for study participants.
Table 2.
Fatty acid composition of CSF fractions normalized to CSF volume.
Table 3.
Fatty acid distribution in CSF fractions.
Table 4.
Fatty acid levels normalized to CSF protein content.
Table 5.
Fatty acid composition of brain-derived nanoparticles from CH, MCI, and AD study participants.
Table 6.
Fatty acid composition of supernatant fluid from MCI and AD study participants.
Table 7.
Free fatty acid levels in CSF from CH, MCI, and AD study participants.
Figure 2.
Free fatty acids were grouped as even-chain SAFAs (A), odd-chain SAFAs (B), total SAFAs (C), total MUFAs (D), n-6 PUFAs (E), n-3 PUFAs (F), total PUFAs (G), and total free fatty acids (H). One-way ANOVA was used to determine group differences and Tukey's multiple comparison test to compare CH (black bar), to MCI (white bar), and AD (gray bar). Data are the mean ± SEM for 68 CH, 38 MCI, and 28 AD study participants with p values indicated on brackets.
Figure 3.
Correlation of DHA levels in clinical groups.
Dependence of free DHA on levels in CSF fractions was determined using the Spearman's ranked correlation coefficient (ρ). A) Free DHA versus DHA levels in SF for CH subjects. B) Free DHA versus DHA levels in the NP fraction for CH subjects. C) Free DHA versus DHA levels in SF for MCI subjects. D) Free DHA versus DHA levels in the NP fraction for MCI subjects. E) Free DHA versus DHA levels in SF for AD subjects. F) Free DHA versus DHA levels in the NP fraction for AD subjects.
Table 8.
Fatty acids that change significantly between diagnostic groups in CSF fractions.