Corticobasal degeneration (CBD) is a progressive neurodegenerative disorder characterized by asymmetric cortical and basal ganglia dysfunction. CBD is classified as a 4R-tauopathy, sharing pathological features with progressive supranuclear palsy (PSP).
| Feature |
Description |
| Motor onset |
Asymmetric rigidity, apraxia (especially hand/limb) |
| Cortical signs |
Cortical sensory loss, alien limb, neglect |
| Movement |
Axial rigidity, dystonia, myoclonus |
| Cognitive |
Frontotemporal dementia, executive dysfunction |
| Speech |
Non-fluent aphasia, speech apraxia |
- Accumulation of 4R tau isoforms
- Neurofibrillary tangles in cortical and subcortical regions
- Astrocytic plaques (characteristic CBD lesion)
- Neuronal loss in substantia nigra and basal ganglia
- Asymmetric cortical atrophy (parietal > frontal)
- Neuronal loss and gliosis
- Ballooned neurons (tau-immunoreactive)
- Reduced synaptic density
- Nigrostriatal pathway degeneration
- Dopaminergic neuron loss in substantia nigra
- Striatal atrophy
- Cholinergic system dysfunction
- Demyelination in corticospinal tracts
- Axonal loss in connecting pathways
- Microglial activation
- H1 haplotype increases risk
- Specific tau mutations linked to CBD
- Tau gene splicing alterations
- Chromosome 17 linked to CBD
- GWAS identified risk variants
- Possible autosomal dominant patterns
- Hyperphosphorylation at multiple sites
- Kinases: GSK3β, CDK5, MARK
- Phosphatase dysregulation
- Microglial activation
- Cytokine release (IL-1β, TNF-α)
- Complement system involvement
- Presynaptic protein loss
- Impaired neurotransmitter release
- Synaptosomal deficits
| Target |
Approach |
Status |
| Tau aggregation |
Small molecule inhibitors |
Preclinical |
| Tau phosphorylation |
Kinase inhibitors |
Phase 1 |
| Neuroinflammation |
Anti-inflammatory agents |
Research |
| Neuroprotection |
Neurotrophic factors |
Preclinical |