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Kennedy's disease: unusual molecular pathologic and clinical features
P J Shaw1, H Thagesen, J Tomkins
1Department of Neurology, University of Newcastle upon Tyne, United Kingdom.
Neurology
|July 23, 1998
Summary
Kennedy's disease (KD) patients exhibited unique pathology, including presenile dementia in one case. This study details neuronal changes and subtle tract pathology, differing from ALS molecular features.
Area of Science:
- Neurology
- Neuroscience
- Genetics
Background:
- Kennedy's disease (KD) is a rare X-linked neuromuscular disorder caused by a mutation in the androgen receptor gene.
- Previous studies have primarily focused on motor neuron degeneration in KD.
Observation:
- Two patients with the Kennedy's disease (KD) mutation were identified in the Newcastle Brain Tissue Bank.
- One patient presented with presenile dementia, a previously undescribed clinical feature in KD.
- Pathological examination revealed neuronal depletion and gliosis in the hippocampus and subcortical gliosis in the prefrontal region in the patient with dementia.
- Immunostaining indicated subtle corticospinal tract pathology in both KD cases.
Findings:
- The neuropathology in the KD patient with dementia involved significant hippocampal and prefrontal cortical changes.
- Unlike Amyotrophic Lateral Sclerosis (ALS), surviving motor neurons in these KD cases lacked ubiquitinated inclusions and altered neurofilament phosphorylation.
- Macrophage marker staining suggested mild pathology in the corticospinal tracts.
Implications:
- This study expands the clinical and pathological spectrum of Kennedy's disease, highlighting cognitive impairment as a potential feature.
- The distinct molecular pathology in KD motor neurons compared to ALS may offer insights into differential disease mechanisms.
- Further research into the mechanisms underlying cognitive decline in KD is warranted.