Table 1.
Summary of selected cases.
Table 2.
Biological process categories overrepresented by the genes related to AD neuropathology (npADGs).
Figure 1.
Hierarchical clustering analysis of CP-AD, P-AD and N samples.
Hierarchical clustering was performed by using the expression values from the genes related to AD neuropathology with P≤0.005 (47 transcripts). Each row represents a single gene and each column a sample (dark blue, CP-AD samples; light blue, P-AD samples; yellow, N samples). Red indicates upregulation, green indicates downregulation, and black indicates no change in expression level comparing to reference sample. Cluster support was given by Bootstrap technic (black, 100% of support; grey, 90–100%; blue, 80–90%; green, 70–80%; light yellow, 60–70%; dark yellow, 50–60%; magenta, 0–50%, red, 0%). CP-AD, clinic-pathological Alzheimer’s disease; P-AD, pathological/preclinical Alzheimer’s disease; N, normal samples (controls).
Figure 2.
Interaction networks of the significant genes and their interacting partners.
(A) Shown are the genes (color nodes) that have, as a function of presence (CP-AD + P-AD) or absence (N) of AD pathology, significantly different correlation of co-expression with their partners. Green nodes indicate genes that are significantly differently expressed between patient groups, while light blue nodes indicate genes that are not significantly differently expressed. Edge colors represent the correlation between a gene and each of its partners. (B) MYC and its interacting partners. Note that the significant genes and their partners form an interconnected network, and despite the interactions involving MYC are not significantly altered, it has a lot of connections, playing an important role as a hub gene. CP-AD, clinic-pathological Alzheimer’s disease; P-AD, pathological/preclinical Alzheimer’s disease; N, normal samples (controls).
Figure 3.
Multivariate (three-gene) discriminators for Alzheimer’s disease (AD) classification.
(A) Discriminator of CP-AD samples (blue) and P-AD samples (red) using the expression values of PTPRN, ULK2, and HES1 genes. (B) Discriminator of CP-AD samples (blue) and P-AD samples (red) using the expression values of CAPRIN1, ULK2, and RFC2 genes. CP-AD, clinic-pathological Alzheimer’s disease; P-AD, pathological/preclinical Alzheimer’s disease.
Figure 4.
Hypothetical model of the gene expression alterations related to neuropathology and clinical manifestation of Alzheimer’s disease (AD).
Gene expression profile changes related to AD pathology are implicated with energy metabolism, oxidative stress, DNA damage and transcriptional regulation. Once established of significant AD pathology, some genes involved with synaptic plasticity, and cell cycle appear to be involved with the clinical outcome of the illness and might represent the molecular mechanisms that underlie the cognitive reserve. CP-AD, clinic-pathological Alzheimer’s disease; P-AD, pathological/preclinical Alzheimer’s disease.