[Corticobasal degeneration (CBD)corticobasal-degeneration) is a rare progressive neurodegenerative disorder characterized by asymmetric cortical and subcortical dysfunction. The striatum, comprising the caudate nucleus and putamen, is critically involved in motor control and is significantly affected in CBD 1.
The striatum contains two major compartmental systems:
- Striosomes (Patches): Matrix-embedded neurochemical compartments involved in limbic functions
- Matrix: The dominant compartment receiving cortical sensory and motor inputs
Both compartments show pathology in CBD, with varying degrees of involvement.
The striatum contains several vulnerable neuronal populations:
- [Medium spiny neurons (MSNs)striatal-medium-spiny-neurons): The principal output neurons, severely affected in CBD
- Cholinergic interneurons: Moderately affected, contribute to movement disorders
- GABAergic interneurons: Show early changes in CBD pathology
CBD is classified as a 4-repeat tauopathy, with characteristic inclusions:
- Cortical basal ganglionic bodies: Tau-immunoreactive inclusions in neurons
- Astrocytic plaques: Distinct astrocytic pathology unique to CBD
- Coiled bodies: Oligodendroglial tau inclusions
The pattern of neuronal loss in CBD includes:
- Asymmetric involvement: One hemisphere more affected than the other
- Cortical-basal pattern: Primary motor cortex and basal ganglia
- Progressive spread: From affected regions to connected areas
CBD is characterized by the selective accumulation of 4-repeat (4R) tau isoforms:
- Alternative splicing dysregulation: Aberrant splicing of MAPT exon 10
- Aggregate seeding: 4R tau seeds propagate throughout connected networks
- Axonal transport impairment: Tau aggregates obstruct transport
Striatal neuronal dysfunction in CBD involves:
- Dopaminergic denervation: Loss of substantia nigra inputs
- Corticostriatal deafferentation: Cortical input loss
- Intrinsic membrane properties: Ion channel dysfunction
Striatal involvement contributes to:
- Akinesia: Reduced spontaneous movement
- Rigidity: Increased muscle tone
- Myoclonus: Brief, involuntary muscle jerks
- Dystonia: Sustained muscle contractions
Striatal-cortical circuit dysfunction leads to:
- Apraxia: Inability to perform learned motor tasks
- Alien limb phenomenon: Feeling that a limb is foreign
- Executive dysfunction: Planning and organization deficits
- Levodopa: Limited efficacy for parkinsonian features
- Botulinum toxin: For focal dystonia
- Physical therapy: Maintain function and prevent contractures
- Tau-directed immunotherapy: Anti-tau antibodies in trials
- Neuroprotective agents: Targeting specific molecular pathways
- Deep brain stimulation: Targeting the globus pallidus internus
- [Corticobasal degeneration (CBD)corticobasal-degeneration)
- [Medium spiny neurons (MSNs)striatal-medium-spiny-neurons)