In frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), recent studies have presumed relationships between cognitive declines and striatal dysfunctions. The striatum contributes to socio-cognitive functions by receiving glutamatergic inputs from the cerebral cortices. However, the vulnerability of these cortico-striatal inputs is unclear in these diseases. This study aimed to evaluate the glutamatergic inputs to the striatum from the cerebral cortices in patients with sporadic TDP-43-related FTLD (FTLDTDP) and ALS (ALS-TDP). We examined 46 consecutively autopsied patients (31 FTLD-TDP and 15 ALS patients) and 10 normal controls. The axon terminals of the glutamatergic cortico-striatal projection neurons were quantified at the striatum using antivesicular glutamate transporter-1 (VGLUT-1) immunohistochemistry. In results, all FTLD-TDP patients displayed marked depletion of VGLUT-1-positive axon terminals in the caudate head and putamen. Particularly, the patients with type C pathology showed a severe loss. The nondemented ALS patients displayed loss of VGLUT-1-positive axon terminals in the putamen, but those were relatively spared in the caudate head. Confocal microscopy revealed TDP- 43 aggregations within VGLUT-1-positive axon terminals in a subset of the patients. Our results indicate marked involvement of glutamatergic striatal inputs from the cerebral cortices in association with sociocognitive declines in a disease spectrum of TDP-43 proteinopathy.
|ジャーナル||Journal of Neuropathology and Experimental Neurology|
|出版ステータス||Published - 09-2017|
All Science Journal Classification (ASJC) codes
- Pathology and Forensic Medicine
- Clinical Neurology
- Cellular and Molecular Neuroscience