Table 1.
Network-predicted risk genes involved in four pathobiological pathways of Alzheimer’s disease (AD)
| Gene | Protein | Description |
|---|---|---|
| Neurotransmitter transport | ||
| MEF2Ca | Myocyte-specific enhancer factor 2C | MEF2C mRNA expression levels were correlated with AD pathology |
| RIMS1 | Regulating synaptic membrane exocytosis protein 1 | An altered protein expression in RIMS1 during AD pathology |
| Beta-amyloid-related biologic process | ||
| APOEa | Apolipoprotein E | Affect Aβ production, aggregation, and clearance |
| CHRNA7 | Neuronal acetylcholine receptor subunit alpha-7 | Bind to Aβ with very high affinity, providing therapeutic insight into AD |
| SORL1a | Sortilin-related receptor | Reduce Aβ generation by trafficking APP away from amyloidogenic cleavage sites |
| ADAM10a | Disintegrin and metalloproteinase domain-containing protein 10 | Constitutive α-secretase in the process of amyloid-β protein precursor (AβPP) cleavage |
| LRP2 | Low-density lipoprotein receptor-related protein 2 | rs3755166 polymorphism within LRP2 gene is associated with susceptibility to AD in the Chinese population |
| Long-term synaptic potentiation | ||
| MAPK1 | Mitogen-activated protein kinase 1 | Beta-amyloid activates the MAPK cascade via hippocampal CHRNA7 |
| PTK2Ba | Protein-tyrosine kinase 2-beta | An in vivo modulator and early marker of Tau pathology |
| Oxidative stress | ||
| FOXO3 | Forkhead box protein O3 | Activate BCL2L11 and FASLG to promote neuronal death and aberrant Aβ processing |
| NOS1 | Nitric oxide synthase | Loss of endothelial NOS promotes p25 production and Tau phosphorylation |
| NFKB1 | Nuclear factor NF-kappa-B p105 subunit | Involve in neuroinflammation, synaptic plasticity, learning, and memory implicated in AD |
| ESR1 | Estrogen receptor | Interact with tau protein in vivo, and prevent glutamate excitotoxic injury by Aβ through estrogen signaling mechanisms |
aGenes have experimental or functional evidence reported in AD transgenic animal models or human-derived samples (see Table S2 and Supplementary Method). The detailed literature data are provided in Table S2