Table 1.
Characteristics of Study Participants.
Figure 1.
Heat map analysis of metabolites in plasma and CSF samples from CN, MCI and AD patients.
Metabolite perturbations were calculated based on the median for each metabolite level of three independent biological replicates of plasma and CSF samples from each study participant. Each row represents a metabolite, and each column depicts a subject. The study groups are color-coded as follows: AD is denoted in red, MCI is denoted in blue, and CN is denoted in maroon. The fold change in metabolite levels is color-coded: red pixels, up regulation; blue, down regulation; yellow, no significant change.
Figure 2.
Plasma and CSF samples have distinct metabolomic profiles between AD, MCI and CN groups.
Two-dimensional score plots of unsupervised principal component analysis (PCA) of the plasma (A) and CSF (B) samples, and orthogonal two partial least squares-discriminant analysis (O2PLS-DA) of plasma (C) and CSF (D) samples from AD (red), MCI (blue) and CN (green) patients. Each sample is labeled with a triangle.
Figure 3.
Unsupervised Principal Component Analysis (PCA) of plasma and CSF samples from CN, AD and MCI subjects.
Each dot corresponds to an individual sample. (A, B): AD – red; CN – blue; (C, D): MCI – red; CN – blue; (E, F): AD – red; MCI- blue.
Figure 4.
Altered metabolic pathways and process networks in plasma and CSF of MCI vs. CN subjects.
The significance of the pathways was evaluated using P values and false discovery rate <0.05. Pathways that are affected in both fluids are colored in red. The ratio depicts the number of affected metabolites to the total number of metabolites in the pathway. TCA – tricarboxylic acid (Krebs) cycle; GABA - γ-Aminobutyric acid; MB – metabolism.
Figure 5.
Canonical pathways and process networks affected in plasma and CSF of AD vs. CN subjects.
The significance of the pathways was evaluated using P values and false discovery rate <0.05. Pathways that are affected in both fluids are colored in red. The ratio depicts the number of affected metabolites to the total number of metabolites in each pathway. FXR - farnesoid X receptor; CFTR - cystic fibrosis transmembrane conductance regulator; VDR - vitamin D receptor; DGAT1 - diacylglycerol acyltransferase 1; nNOS – neuronal nitric oxide synthase; UMP - Uridine monophosphate; HETE - hydroxyeicosatetraenoic acid; HPETE - hydroperoxyeicosatetraenoic acid; BS – biosynthesis.
Figure 6.
Altered metabolic pathways and process networks specifically affected either in plasma or in CSF of AD vs. MCI subjects.
The significance of the pathways was evaluated using P values and false discovery rate <0.05. GABA - γ-Aminobutyric acid; nNOS – neuronal nitric oxide synthase; CFTR - cystic fibrosis transmembrane conductance regulator; VDR - vitamin D receptor; HETE - hydroxyeicosatetraenoic acid; HPETE - hydroperoxyeicosatetraenoic acid.
Figure 7.
Venn diagram illustrating shared and uniquely affected pathways in plasma and CSF of MCI, AD and CN individuals.
Common pathways are defined.