Table 3 Clinical relevance of the core DHN to dementia through biomarker-guided analysis
Target candidate | Pathway membership | Disease association | Biomarker type | Brain tissue specificity | Cell-type specificity |
|---|---|---|---|---|---|
MAPK3 | Alzheimer’s disease, Prion disease, Type II diabetes mellitus, Insulin signaling pathway, Long-term potentiation | Autism | CSF increased levels AD (PMID: 22145083, 19625747), Phosphorylation (PMID: 19233276, 16920298, 17612901), Alterations in lymphoblasts of AD patients (PMID: 19158936) | Left ventricle, Right ventricle, Brain stem | Microglia, Astrocytes, Neurons |
NOS1 | Alzheimer's disease, Long-term depression, Calcium signaling pathway | Parkinson's disease, Alzheimer's disease, Diabetes Mellitus type II | Nitric oxide overproduction (PMID: 20804853), nNOS signaling initiated in interneurons (PMID: 16758165), Increased expression of nNOS isoforms in astrocytes (PMID: 12384247) | Substantia nigra, Forebrain, cerebral white matter, Limbic system | Astrocytes, Neurons |
CREB1 | Huntington's disease, Cholinergic synapse | Alzheimer's disease | Impaired CREB phosphorylation (PMID:22119240) | Substantia nigra, Brain stem, Sub-commissural organ, Brain ventricle, Cerebral gray matter, Cerebral white matter, Forebrain, limbic system | Hippocampal neurons, Dendate gyrus |
JUN | GnRH signaling pathway, Neurotrophin signaling pathway, MAPK signaling pathway | Cognitive performance | Prolonged expression of c-Jun (PMID:8774439), Increased immuno-reactivity (PMID:8313943) | Sub-commissural organ, Brain ventricle, Cerebral gray and white matter | Neurons, Microglia, Substantia nigra |